EFFECT OF POLYMERS AND STARCH ON PHYSICAL PROPERTIES OF LYOPHILIZED ORALLY DISINTEGRATING TABLETS

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Contents

ORAL PRESENTATION 7

COMPATIBILITY CHARACTERIZATION OF GENTAMICIN-NIGELLA SATIVA FUSION AS A FUTURE

'GREENER' PHARMACEUTICAL INTENDED FOR ORTHOPAEDIC INFECTION 8

EFFECT OF POLYMERS AND STARCH ON PHYSICAL PROPERTIES OF LYOPHILIZED ORALLY

DISINTEGRATING TABLETS 10

GREEN APPROACH TOWARDS BIOENHANCED CURCUMIN: PROCESS ANALYTICAL TECHNOLOGY (PAT) ENABLED SCALE UP STUDIES OF CURCUMIN SOLID SOLUTION USING HOT MELT EXTRUSION 12 ANTIBIOTICS PSEUDOPOLYMORPHISM STUDY BY PXRD AND THERMAL ANALYSIS 14 FORMULATION AND EX-VIVO EVALUATION OF TRANSDERMAL PATCHES AND STUDY ON PENETRATION ENHANCEMENT EFFECT OF BUCHANANIA LANZAN (SPRENG) SEED OIL 16 ADVANCES IN PROCESS TECHNOLOGY FOR RAPID PRODUCTION OF PHARMACEUTICAL

NANOSUSPENSIONS 18

A NOVEL METHOD FOR TASTE MASKING OF IBUPROFEN PARTICLES USING NANOPARTICLES OF

PHARMACOLOGICALLY INERT MATERIALS 21

UNIFORM PHARMACEUTICAL MICROPARTICLES WITH WELL-DEFINED PROPERTIES PRODUCED BY A

NOVEL MICROFLUIDIC JET SPRAY DRYER 23

NOVEL ORAL SNEDDS OF ARTEMETHER: THE FUTURE CLINICAL OUTCOME 24

APPLICATION OF HIBISCUS ESCULENTUS (OKRA) GUM IN SUSTAINED RELEASE DOSAGE FORM OF

PROPRANOLOL HYDROCHLORIDE 25

FUTURE GREENER BIOPHARMACEUTICAL (NBP) TO CENTRAL NERVOUS SYSTEM (CNS): EFFECT OF POLY(D,L-LACTIC-CO-GLYCOLIC ACID) AND CHITOSAN MOLECULAR WEIGHT ON FORMULATION. 26 FORMULATION DEVELOPMENT, EVALUATION AND ANTI-INFLAMMATORY EFFECTS OF KETOPROFEN

CREAM ON RHEUMATOID ARTHRITIS PATIENTS 28

GREEN TECHNOLOGY EXTRACTION OF BIOACTIVE COMPOUNDS FROM ZINGIBERACEAE PLANTS USING

SFE 29

EXTRACTION SELECTIVITY-A NEW TOOL FOR GREEN PROCESS ANALYSIS AND DESIGN OF SOLID-LIQUID

EXTRACTOR 30

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GREEN PROCESS DEVELOPMENT OF HERBAL AND/UPSTREAM PHYTOCHEMICAL PRODUCTS IN DRUG

DISCOVERY AND DEVELOPMENT 32

1H NMR AND UV/ VISIBLE SPECTROPHOTOMETERIC STUDY OF THE ARSENIC COMPOUNDS WITH GLUTATHIONE IN BLOOD AND AQUEOUS SOLUTION A TOXICOLOGICAL AND PHARMACOLOGICAL

PERSPECTIVE. 37

STRUCTURAL MODIFICATION OF A NATURAL POLYMER CASSIA TORA BY MICROWAVE ASSISTED GRAFTING TECHNIQUE INTENDED TO USE SUSTAINED RELEASE MATRIX TABLET FORMULATION 38 DOCKING STUDIES OF AEGLE MARMELOS PLANT COMPOUNDS AGAINST GASTRIC CANCER CELL

SURFACE RECEPTOR PROTEINS – CD340 AND FGFR2B 40

DESIGN AND SYNTHESIS OF NOVEL FLAVONOIDS AS GABAA RECEPTOR LIGANDS 41 PREPARATION, CHARACTERIZATION AND REDUCTION OF BURST RELEASE OF BSA FROM

BIODEGRADABLE PLGA MICROSPHERES 42

TURNING WEEDS INTO DRUGS: THE PROSPECT OF MIMOSA PUDICA LINN. ON DIABETES MELLITUS, IN

VITRO 45

EFFECTS OF BACCAUREA ANGULATA FRUIT JUICE ON PLASMA LDL AND HDL CHOLESTEROL AND OXIDIZED LDL CONCENTRATIONS IN NORMO- AND HYPERCHOLESTEROLEMIC RABBITS 47 ISOLATION OF A PROMISING ANTIDIABETIC COMPOUND FROM THE LEAVES OF TETRACERA INDICA MERR., AND IN VIVO TOXICOLOGICAL STUDIES IN DIABETES INDUCED EXPERIMENTAL ANIMALS 48 KNOWLEDGE PORTAL AND MOBILE APPLICATION FOR ETHNOBOTANICAL AND PHYTOCHEMICAL

INFORMATION OF ASIA 51

CYTOTOXIC ACTIVITY OF LUVUNGA SCANDENS PLANT ON HUMAN CANCER CELL LINES 53 PERSONAL DATA PROTECTION IN CLINICAL TRIAL IN MALAYSIA: A QUEST FOR LEGAL AND

REGULATORY FRAMEWORK 55

DETECTING AND MEASURING EURYCOMANONE LEVELS IN VARIOUS TONGKAT ALI PRODUCTS 56 REGULATORY CHALLENGES IN THE DEVELOPMENT OF PALM OIL-BASED INJECTIONS FOR

PHARMACEUTICAL USE 57

POTENTIAL HEALTH BENEFITS OF TRADITIONAL HERBAL FORMULA, DIABECINE™ 58

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MOLECULAR MECHANISMS OF ANTI-OSTEOPOROTIC AND ANTIOXIDANT EFFECTS OF VIRGIN

COCONUT OIL IN OVARIECTOMIZED RATS 59

EFFECTS OF COSMOS CAUDATUS ON BONE FRACTURE HEALING IN OVARIECTOMISED RATS: MICRO-

CT ANALYSIS 60

PROMOTION OF HUMORAL IMMUNITY BY AN AYURVEDIC HERBAL PREPARATION, SARIBADYARISTA 63 COMPARATIVE NEUROPROTECTIVE ACTIVITY OF BENINCASA HISPIDA SEEDS AND MESOCARP AGAINST

NEURODEGENARATIVE DISORDER, DEMENTIA 65

PROPERTIES IMPORTANT FOR THE GREEN PROCESSING OF BIOMATERIAL-RELATED COMPOUNDS

WITH SUPERCRITICAL CARBON DIOXIDE 67

ENVIRONMENTAL IMPACT ASSESSMENT FROM ENERGY CONSUMPTION IN EARLY PROCESS DESIGN

OF A LARGE-SCALE MONOCLONAL ANTIBODY PRODUCTION 68

SEPARATION SPHERICAL ORGANIC MACROMOLECULE COMPOUND BY UF/MF MEMBRANE 71 AN ATTEMPT TO ISOLATE INDUSTRIALLY IMPORTANT MICROORGANISM FROM DIVERSE SAMPLES

COLLECTED FROM SEMELING, KEDAH, MALAYSIA 72

CHALLENGES AND OPPORTUNITIES IN THE MANAGEMENT OF HOUSEHOLD WASTE MEDICINES FOR

THE PHARMACEUTICAL COMPANIES IN BRAZIL 74

POSTER PRESENTATION 75

FORMULATION AND IN-VITRO CHARACTERIZATION OF FLOATING SUSTAINED-RELEASE TABLETS OF

METFORMIN HYDROCHLORIDE 76

FORMULATION AND OPTIMIZATION OF RALOXIFENE LOADED NANOTRANSFERSOMES BY RESPONSE

SURFACE METHODOLOGY FOR TRANSDERMAL DRUG DELIVERY 79

INFLUENCE OF CELLULOSE POLYMER TYPES ON IN VITRO RELEASE OF DOMPERIDONE SR TABLETS 83 BUCHANANIA LANZAN SPRENG SEEDS MUCILAGE: IN VITRO-IN VIVO MUCOADHESIVE STRENGTH

ASSESSMENT 84

EFFECTIVE AND CONTROLLED TRANSDERMAL DELIVERY OF LERCANIDIPINE HYDROCHLORIDE: SYSTEM

DESIGN AND CHARECTERIZATION 87

FORMULATION AND STABILITY TESTING OF GENTAMICIN-NIGELLA SATIVA EMULSIONS FOR OSTEO-

HEALING APPLICATION 88

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OPTIMIZATION OF PITAYA SEED EXTRACTS- BASED NANOCOSMETICEUTICAL FORMULATION USING

RESPONSE SURFACE METHODOLOGY (RSM) 89

REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF MEFENAMIC

ACID IN HUMAN PLASMA USING LIQUID-LIQUID EXTRACTION TECHNIQUE 91

PULSATILE DRUG DELIVERY SYSTEM OF IBUPROFEN AND FAMOTIDINE 92

STOMACH SPECIFIC DELIVERY OF ANDROGRAPHOLIDE FROM FLOATING IN SITU GELLING SYSTEM 94 NEW GAHARU AROMATIC PRODUCTS FROM AGARWOOD OLEORESIN AND SOLID RESIN 95 DEVELOPMENT OF HALAL MODIFIED RELEASE GLICLAZIDE 60 MG TABLETS BY CENTRAL COMPOSITE

DESIGN AND PRODUCTION BY DIRECT COMPRESSION 97

ANTIOXIDANT ACTIVITY STUDIES OF NOVEL SCHIFF AND MANNICH BASES 99 SOLUBILITY PREDICTION AND ISOTHERMAL ANTISOLVENT CRYSTALLIZATION MODELING AND

OPTIMIZATION 100

A GREEN APPROACH TO INVESTIGATE THE EFFECT OF SOLVENTS ON THE CRYSTALLIZATION OF

MEFENAMIC ACID POLYMORPHS 101

ASSESSMENT OF THE ANTIBACTERIAL ACTIVITY OF CRUDE ALKALOIDAL EXTRACTED FROM SEEDS AND

LEAVES OF SWIETENIA MACROPHYLLA KING. 103

CHANGES IN THE ANTIOXIDANT ENZYMES AND INFLAMMATORY MARKERS FOLLOWING ADMINISTRATION OF BELIMBING DAYAK (BACCAUREA ANGULATA) FRUIT JUICE ON EXPERIMENTAL

RABBITS FED WITH CHOLESTEROL DIET. 104

GC – MS ANALYSIS AND ANTIBACTERIAL ACTIVITY OF ESSENTIAL OIL FROM ORTHOSIPHON

THYMIFLORUS ROTH. 106

EVALUATION OF PELTOPHORUM ROXBURGHII FOR ITS HEMATOLOGICAL PARAMETERS AND

ERYTHROCYTE SEDIMENTATION 109

BIOMONITORING METALS IN LEECHES (HIRUDINARIA MANILLENSIS) – A STEP TOWARDS ITS

IMMEDIATE APPLICATION IN TRADITIONAL MEDICAL TREATMENTS 110

IN VITRO ANTIMICROBIAL EFFECT OF GENTAMICIN-NIGELLA SATIVA FUSION EMULSION AGAINST BIOFILM PRODUCING STRAIN S. AUREUS, P. AERUGINOSA AND S. EPIDERMIDIS 111

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CYTOTOXIC ACTIVITY OF FLOWERING AND NON-FLOWERING STAGES OF MELASTOMA DECEMFIDUM

ROXB. ON CANCER CELL LINES 114

INVESTIGATION OF APOPTOTIC EFFECTS OF DICHLOROMETHANE EXTRACT OF AGLAIA EXIMA LEAVES

ON HUMAN CANCER CELL LINES 116

CYTOTOXIC ACTIVITY OF JUSTICIA GENDARUSSA LEAF EXTRACTS ON MCF-7 BREAST CANCER CELL LINE 117 EFFECTS OF GARCINIA MANGOSTANA ON ADIPOCYTE DIFFERENTIATION AND GLUCOSE UPTAKE

REGULATION IN 3T3-L1 CELLS 119

PREVENTIVE ANTIOXIDANT EFFECT OF TOCOTRIENOL ON STRESS-INDUCED GASTRIC MUCOSAL LESIONS AND ITS RELATION TO INDUCIBLE NITRIC OXIDE SYNTHASE EXPRESSION 120 SOLUBILITY PREDICTION OF L-ASCORBIC ACID IN SOLVENTS USING NON-EMPIRICAL METHOD 121 SKIN PENETRATION- ENHANCING EFFECT OF NATURAL OILS: IN VITRO STUDY 123 HPLC ANALYSIS AND BIOKINETIC STUDIES OF PYRAZINAMIDE IN FEMALE VOLUNTEERS 124 AN OBSERVATIONAL STUDY COMPARING EFFICACY AND SAFETY OF BASAL BOLUS INSULIN REGIMEN AND TWICE DAILY PREMIXED INSULIN REGIMEN AMONG DIABETES MELLITUS TYPE 2 PATIENTS 125 GENERAL PUBLIC KNOWLEDGE AND PERCEPTION TOWARDS HERBAL BEVERAGES IN KUANTAN,

MALAYSIA 126

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ORAL

PRESENTATION

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COMPATIBILITY CHARACTERIZATION OF GENTAMICIN-NIGELLA SATIVA FUSION AS A FUTURE 'GREENER' PHARMACEUTICAL INTENDED FOR ORTHOPAEDIC INFECTION

Ahmad Fahmi Harun Ismail, Farahidah Mohamed, Nazri Mohd Yusof, Mohd Affendi Mohd Shafri Department of Pharmaceutical Technology, Kulliyyah of Pharmacy, International Islamic University

Malaysia, Kuantan Campus, Malaysia Email: fahmi.iium.kntn@gmail.com

The medical potentials of natural product have been extensively exploited nowadays to reduce many adverse effects associated with the conventional medicine. However, the issue of compatibility has become a major concern amongst the researchers in developing any drugs and active pharmaceutical ingredients. In this study, the fusion between the oil of Nigella sativa L. (or Habbatus Sauda) and gentamicin powder was sent for sterilization using gamma irradiation at 10 kGy - 40 kGy. This fusion was developed and intended to be used for the treatment of osteomyelitis. The pre and post gamma irradiation evaluation was carried out by using Fourier Transform Infrared Spectroscopy (FTIR) to observe for any physical changes both for the raw materials and the fusion. The data from Differential Scanning Calorimeter (DSC) was parallel with FTIR in indicating no physical and chemical interactions initiated during the process of sterilization. For DSC, this was done by conforming the melting point of pre and post gamma irradiation for both gentamicin powder and N. sativa oil. Nonetheless, the fusion was not able to be evaluated using DSC due to rapid disintegration of the oil when subjected to a temperature higher than 120^oC. In addition, the surface and the interfacial tensions between the oil and the gentamicin solution were measured to support the pre and post evaluation of gamma irradiation on the API. The N. sativa oil was further evaluated by using Thin Layer Chromatography (TLC) to observe the retention factor (Rf) for both pre and post gamma irradiation by employing the mobile phase of dichloromethane and hexane (1:1). The Rf value showed similarity for N. sativa oil in both conditions indicating the oil was stable enough to undergo the gamma sterilization. Gentamicin however could not be evaluated using TLC due to the issue of insolubility in any organic solvents. . Encapsulation of N.

sativa oil by using FDA-approved polymer, PLGA, was carried out to formulate the sustained release microparticles. The encapsulation was carried out by employing the single emulsion solvent evaporation method. Having the characteristic of biodegradable and biocompatible in nature, PLGA is the best candidate to be used as the encapsulating agent. Three different parameters were studied i.e. the molecular weight of PLGA, the method of homogenizing and the amount of N. sativa oil loaded during the fabrication process. The external morphology and the particle size were observed and analyzed by using scanning electron microscopy (SEM) and laser diffraction respectively. The size of the fabricated particles ranging from 5.83 µm ± 0.04 up to 147.71 µm ± 3.18 was observed mostly with smooth but irregular shape. Furthermore, the percentage of oil loading for every formulations was evaluated by using spectrophotometry with the highest loading was recorded at 91.90 % and the lowest with the value of 56.94%. However, the oil loading from two formulations were unable to be evaluated due to

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the particle stability and the degree of hydrophobicity issues. Manipulating the potential of this fusion is believed to open a new promising method in treating osteomyelitis. Taking into consideration the ability to encapsulate the N. sativa oil by using PLGA, this ongoing research can provide an envision towards the possible 'greener' opportunities to be explored in future.

Keywords: Nigella sativa oil, Gentamicin, PLGA, Osteomyelitis

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EFFECT OF POLYMERS AND STARCH ON PHYSICAL PROPERTIES OF LYOPHILIZED ORALLY DISINTEGRATING TABLETS

Kai Bin Liew, Michael Odeniyi, Kok Khiang Peh Universiti Sains Malaysia, Malaysia

Email: liewkaia@yahoo.com

Orally disintegrating tablet (ODT) is a user friendly and convenient dosage form. The study aimed to investigate the effect of polymers and wheat starch on the physical properties of lyophilized ODT using sildenafil citrate as a model drug. Three polymers (hydroxypropylmethyl cellulose (HPMC), Carbopol 934P and Eudragit EPO) and wheat starch were used as matrix forming materials in preparation of lyophilized ODT. The polymeric dispersion was casted into a mould and kept in a freezer at -20˚C for 2 hours before freeze dried for 6 hours. The ODT surface morphology was observed under scanning electron microscope and evaluated for hardness, friability, disintegration time and wetting time.

The image of lyophilized ODT is shown in Fig 1. The concentration of the polymers influenced the integrity and strength of the tablets. Increasing HPMC and Carbopol concentrations resulted in higher hardness. In contrast, Eudragit EPO was unable to form tablet with sufficient hardness at various concentrations. The hardness of lyophilized HPMC ODT was comparatively higher than that of Carbopol ODT at the same concentration level. ODT of less friable was obtained. Wheat starch acted as binder improving the hardness of ODTs. However, the disintegration time of ODTs was prolonged when the concentration of polymers and wheat starch increased, attributed to increase in hardness of ODT. All the ODT formulations wetted within 6 s. ODT comprising of HPMC and wheat starch at ratio of 2:1 was found to be optimum based upon the physical properties. Incorporation of sildenafil citrate granules into the formulation significantly increased the tablet hardness (0.65 ± 0.07 kg), wetting time (9.60 ± 1.17 s) and in-vitro disintegration time (150.33 ± 7.39s). The wetting time test is presented in Fig 2. The lyophilized tablets were friable (0.62%). More than 80% of the drug was released within 30 minute (Fig 3). Scanning electron micrographs of the fracture plane of the final formulation is shown in Fig 4.

In conclusion, lyophilized sildenafil citrate ODT with satisfactory hardness, low friability and fast disintegration time was successfully developed from affordable excipient using simple processing steps.

The manufacturing method is amicable for upscale.

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Keywords: Lyophilization, Orally Disintegrating Tablet, Sildenafil Citrate, HPMC, Carbopol, Wheat Starch

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GREEN APPROACH TOWARDS BIOENHANCED CURCUMIN: PROCESS ANALYTICAL TECHNOLOGY (PAT) ENABLED SCALE UP STUDIES OF CURCUMIN SOLID SOLUTION

USING HOT MELT EXTRUSION

Preshita Desai¹, Vinod Gokarna¹, Vinita Deshpande¹, Vandana Patravale¹, Chaitrali Kulkarni², Anant Paradkar²

1Institute of Chemical Technology, India, ²University of Bradford, United Kingdom Email: preshita1712@gmail.com

The present study aims at scale up optimization of curcumin solid solution pre-developed on Twin Screw Hot Melt Extruder Haake MiniLab (Thermo Scientific) equipped for batch process to Twin Screw Pharma lab 16 mm (Thermo Scientific) enabling continuous process, wherein PAT analysis was used as an efficient tool to understand mechanistic formation of amorphous solid solutions and to optimise critical process parameters. Owing to the strong antioxidant potential, curcumin exhibits arena of pharmacological activities but its effective clinical use is limited because of its extremely meager oral bioavailability resulting from chemical instability at neutral and basic pH and negligible aqueous solubility (maximum11 ng/ml in aqueous buffer pH 5.0).

The rationalised use of hot melt extrusion technology herein involves melting of hydrophilic excipients above glass transition temperature where they act as a solvent for the drug and thus forming an amorphous one phase system achieving enhanced aqueous solubility and in turn improved oral bioavailability. The scale up studies were performed by taking lead from the pre-optimised batch on Haake MiniLab (internal volume capacity of 7 cm³) wherein the drug to excipient ratio was optimised to 1:3 and the excipient matrix comprised hydrophilic polymers Kollidon® VA 64 and Soluplus® with VBP 5 as a solubilizer. For scale up, critical process parameters viz. process temperature, time, feed rate, screw speed, shear etc. were optimised under PAT screening at various mixing zones.

The optimised scaled up formulation indicated almost 13 fold improvement in drug dissolution at the end of 1 hour as compared to plain curcumin and exhibited significant similarity factor (F2 value) of 91.23% to that of pre-developed formulation(Fig.1).The PAT analysis of optimised formulation using fourier transform infrared spectroscopy, raman spectroscopy, differential Scanning calorimetry, X-ray diffraction and scanning electron microscopy indicated formation of solid solution exhibiting strong intermolecular hydrogen bonding and complete amorphization of drug. This can be significantly attributed to temperature dependent enhancement in saturation solubility of drug in excipient matrix followed by shear assisted mixing helping towards stability and formation of molecularly dispersed solid solution. Further, stability of formulation is under assessment as per ICH guidelines. Thus successful scale up was achieved enabling industrial feasibility of developed technology towards bioenhancement of curcumin.

Keywords: Hot melt extrusion, solid solution, PAT, bioenhancement

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Figure 1: In vitro dissolution profiles of curcumin, physical mixture and hot melt extruded formulation Data expressed as mean

± SD, n = 3

Figure 2: PAT analysis of curcumin solid solution during hot melt extrusion a. X-ray diffraction analysis b. Raman spectroscopy

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ANTIBIOTICS PSEUDOPOLYMORPHISM STUDY BY PXRD AND THERMAL ANALYSIS

Ilma Nugrahani¹, Silvana Anggraeni¹, Pusparani Khrisnamurti¹

1Bandung Institute of Technology (ITB), Indonesia Email: ilma_nugrahani@fa.itb.ac.id

A lot of solid drug materials have water/organic solvent molecule in their three-dimension crystal structure, which is commonly called as “hydrate”/”solvate” or “pseudopolymorphism”. Hydrate/solvate form of the drug materials has different physicochemical properties of solids compared their anhydrate form, such as density, solubility, compressibility, hygroscopicity, etc. Difference in solubility can affect to dissolution profile and ultimately bioavailability of a drug in the body. So, research on hydrate/solvate form, stability, and change/transformation is needed to obtain important information related preformulation a drug dosage form. Powder Xray Diffractometry (PXRD) is one of important instruments for studying the solid properties and crystal structure, that commonly used to analyse the hydrate and its transformation and usually supported by thermal analysis such as Differential Scanning Calorimetry (DSC) or Differential Thermal Analysis (DTA). This research was aimed to observe the stability of hydrate of cephadroxil, cephalexin, and clindamycin HCl. Their molecule structure describe in Figure 1 while the 3 dimensional of clindamycin HCl hydrate and solvate structure showed in Figure 2. In the first experiment, grinding was done to release hydrate from the crystal lattice of cephadroxil and cephalexin monohydrate; then storage in desiccator with RH 70% and 90% conducted to observe the process of hydrate returned into the crystal lattice. At the second part of this research, the pseudopolymorphism of clindamycin HCl was observed through recrystallization with various percentages of ethanol. Recently reported the formation of clindamycin solvate from ethanol 2:5 without information about the effect of ethanol concentration on the solvate form, and without its diffractogram/thermal behaviour. Storage for 24 hour at ambient temperature was done to observe the hydrate and hydrate solvate stability with PXRD and DTA. The diffractograms showed that the hydrate of cephadroxil and cephalexin released after grinding thoroughly (Figures 3 and 4) that also explained that the hydrate of cephadroxil can return after storage in high humidity, meanwhile hydrate of cephalexin cannot. The loss of hydrate of antibiotics after grinding confirmed by DSC (Figure 5). The recrystallization of clindamycin HCl yielded hydrate from 50% ethanol; the monohydrate ethanol solvate yielded by solvent 70%; meanwhile 95%

ethanol produced a monohydrate-ethanol crystal that analysed by PXRD (Figure 6) and DTA (Figure 7).

The evaluation after storage showed that hydrate and solvate form of clindamycin hcl are unstable, even in the ambient temperature, which proved by PXRD and DTA clearly (Figures 6 and 7).

Keywords: Antibiotics, pseudopolymorphism, PXRD, thermal analysis

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FORMULATION AND EX-VIVO EVALUATION OF TRANSDERMAL PATCHES AND STUDY ON PENETRATION ENHANCEMENT EFFECT OF BUCHANANIA LANZAN (SPRENG) SEED

OIL

Rajesh Dodia¹, Sudarshan Singh², Yogesh V Ushir³, Sunil B Bothara⁴

1Laxminarayan Dev College of Pharmacy, India, ²HSBPVTS College of Pharmacy, India,

3S.B.T College of pharmacy, India, ⁴Bagwan college of Pharmacy, India Email: rajdodia7@gmail.com

The aim of the present work was to evaluate the permeation enhancement properties of Buchanania lanzan Spreng seed oil. Ethyl cellulose (EC) transdermal patches of Glipizide using some natural oils as penetration enhancers such menthol oil and B. lanzan Spreng seed oil was developed (Table 1). Patches were evaluated for thickness, moisture content of film, moisture uptake, folding endurance and percentage elongation. Further surface morphology, effect of drug loading and penetration enhancers on the in vitro permeation of drug through rat skin was investigated.

Preliminary studies, the EC films were found brittle. The study revealed that, addition of Di-n-butyl phthalate produce smooth uniform and flexible films.

In order to understand the partition phenomena of drug between skin, in vitro partition study [3] was performed in triplicate and logarithmic value was found 1.446 ± 0.07. It indicates that drug possesses sufficient lipophilicity for percutaneous transfer. The results of SEM (Figure 1) analysis for optimized formulation F4 showed that the drug has been uniformly distributed through the patches. Drug- excipient interaction was studied by FTIR and DSC technique. The result of interaction study is presented in figure 2a, 2b and 2c, spectra of drug and transdermal patch showed no characteristic interaction.

Incorporation of natural oils enhanced the moisture content, moisture uptake capacity and permeation of Glipizide across skin barriers (Table 2). Among the penetration enhancers used, B. lanzan Spreng seed oil found most effective. The drug content (Table 2) of all the formulations was ≥ 98.37 % with low standard deviations (≤ 1.2 %) indicating that the method employed to prepare films in this study was capable of giving films with uniform drug distribution and insignificant batch variability (p>0.001). The cumulative amount of drug permeated/cm2 was plotted against time and the steady state permeation flux (J) was calculated from the slope of linear portion of the curve (Table 2). When the permeation studies were conducted using cellophane membrane as the permeation barrier, except B. lanzan Spreng seed oil, which showed a flux of 185.38 mcg/cm2/hr, menthol oils did not improve (p>0.05) flux the values. When rat abdominal skin was used as permeation barrier, comparison of flux value of F5 with flux values of formulations with essential oils (F1 to F4) indicated a significant (p< 0.001) increase in the permeation of drug. It was concluded that stable and effective Glipizide transdermal patches can be prepared using seed oils as penetration enhancers.

Keywords: Penetration enhancers, Natural oils, Ex vivo study

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Figure 1: SEM of Optimized batch with B. lanzan spreng seed oil at various magnifications

Figure 2a: FTIR spectra of (A) Glipizide (B) Drug Loaded Polymeric Patch with Menthol Oil

Figure 2b: FTIR spectra of (A) Glipizide (B) Drug Loaded Polymeric Patch with B. lanzan Spreng seed oil

Figure 2c: DSC spectra of (A) Glipizide (B) Optimized Formulation in Drug Loaded Polymeric Patch with B. lanzan Spreng seed oil

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ADVANCES IN PROCESS TECHNOLOGY FOR RAPID PRODUCTION OF PHARMACEUTICAL NANOSUSPENSIONS

Shahzeb Khan¹, Syed Mukaram Shah¹, Jahangir Khan¹, Marcel de Matas², Jamshed Anwar³, Smitha Plakkot⁴, Syed Muhammad Hassan Shah⁵

1Department of Pharmacy, University of Malakand, Dir Lower KPK, Pakistan, ²AstraZeneca, Charter Way, Macclesfield SK10 2NA, United Kingdom, ³Department of Chemistry, Faraday Building, Lancaster University, Lancaster LA1 4YB, United Kingdom, ⁴Institute of Life Sciences research, University of Bradford, United Kingdom, ⁵Department of Pharmacy, Sarhad University KPK, Peshawar, Pakistan

Email: shahzeb_333@hotmail.com

Developments in nanotechnology have the potential to address a number of issues currently experienced in the development of new chemical entities (NCEs). One such problem affecting the likelihood of a new drug reaching the market is low aqueous solubility and more than 70% of the drugs coming from high throughput screening are poorly water soluble. Amongst a number of technologies employed for addressing the issue of poor water solubility, nanoparticles technology has become the most promising approach. Manufacturing processes to generate nanoparticles can be categorized as top down and bottom-up processes. These methods have however some issues including long processing time, broader size distribution and uncontrolled particle growth. We report here the application of a low energy anti solvent crystallization and a very effective and reproducible wet milling method (DENA DM100) for preparing stable nanocrystals of the poorly soluble oral hypoglycemic drug glibenclamide (Figure 1 (A). Glibenclamide, nanocrystals were prepared by controlled crystallization by infusing 1 mL of drug solution (5 mg/mL) dissolved in poly (ethylene glycol) 400 (PEG-400) at a rate of approximately 100 mL/min into 9 mL of a stabilizer solution composed of HPMC 15 cP (1% w/v) and PVP K-30 (0.5% w/w).

The nanocrystals of glibenclamide were also prepared by use of the DENA DM100 size reduction system.

The DENA DM100 system comprises a fast-rotating conical rotor (1500 rpm) constructed from a soft polymer and the grinding media (0.2 mm yttrium-reinforced 115 zirconium beads) are housed inside indentations within the rotor that form a narrow gap between the outer sleeve and rotor. The high shear and turbulence generated within this narrow gap provide the potential for rupture and shearing of particles, leading to an ultrafine product in the submicrometer size range. The drug substance was mixed with the aqueous stabilizer solution (150 mL) being composed of (0.1% w/w), PVP-K30 (0.5%

w/w), and HPMC (0.5% w/w) then made up the final volume to 250 mL suspension containing 2.0%

(w/w) of the drug material. The resultant suspension was then placed into the feedstock hopper of the size reduction system. The suspension was processed for 60 min by recycling through the size reduction chamber. In-process samples were taken at intervals of 5, 10, 15, 30, 45, and 60 min. The particle size measurements of the produced nanocrystals by controlled crystallisation and wet melling were carried out using dynamic light scattering (DLS) on a Zetasizer Nano instrument which resulted in 298 ± 1.5 and 300.0 ± 2.0 respectively (Figure 1, D and E). There was observed a decrease in particle size with the

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increase in milling time (Figure 1 (E)). The particles morphology, crystallinity and melting point were determined by TEM (Figure 1 (B and C), PXRD and DSC respectively. PXRD and DSC studies confirmed the crystalline nature of the produced nanoparticles which are preferable forms for dosage form design (Figure 1 (F and G)). There was observed a decrease in PXRD peaks intensity and low melting point and heat of fusion for the processed glibenclamide particles which is because of the reduction in particle size and small packing density . Stability studies demonstrated for a period of one month did not show any significant crystal growth and all the nanocrystals within the suspensions were homogeneously distributed (PDI: < 0.1). The produced nanocrystals demonstrated marked increase in the dissolution rate compared to the microsuspensios and marketed formulations (Figure 1 (H)). In summary both the technologies employed for production of drug nanocrystals were found very much effective and successful to produce stable nanocrystals with narrow size distribution with subsequent higher dissolution rate.

Keywords: Glibenclamide, Nanocrystals, Crystallisation, Wet milling, Dissolution

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Figure 1: SEM images of raw glibenclamide; (A) TEM images of crystallised (B); and milled glibenclamide (C) Particle size distribution of crystalised glibenclamide (D); and milled glibenclamide (E). PXRD spectrum of processed and unprocessed glibenclamide (F). DSC profile of unprocessed and unprocessed glibenclamide particles (G) Comparative dissolution profile of glibenclamide nanocrystals with the Marketed formulations (H).

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A NOVEL METHOD FOR TASTE MASKING OF IBUPROFEN PARTICLES USING NANOPARTICLES OF PHARMACOLOGICALLY INERT MATERIALS

Shahzeb Khan¹, Marcel de Matas², Jamshed Anwar³, Farhana Karim⁴, Syed Mukaram Shah¹, Jahangir Khan¹, Syed Muhammad Hassan Shah⁵

1Department of Pharmacy, University of Malakand, Dir (L) KPK, Pakistan, ²AstraZeneca, Charter Way, Macclesfield SK10 2NA, UK, ³Department of Chemistry, Faraday Building, Lancaster University, Lancaster

LA1 4YB, UK, ⁴Institute of Life Sciences research, University of Bradford UK,⁵Department of Pharmacy, Sarhad University KPK, Peshawar, Pakistan

Email: shahzeb_333@hotmail.com

Some drugs are unpalatable due to their unpleasant bitter taste, creating compliance issues, especially in the pediatric population [1]. Technologies for taste masking involve the formation of a barrier between the drug and taste receptors in the buccal cavity [2]. This can be accomplished by coating of drug to retard release in mouth. There has been reported a range of methods for taste masking of the bitter drugs including use of flavours and sweeteners, use of lipoprotein, numbness of taste buds, microencapsulation and coating by polymers [3]. Nonetheless these techniques have some issues which include stability, drug release at intestinal pH and less cost effective. The most promising technique to address the issue of bitter taste of many drugs includes adsorption of inert nanoparticles onto the drug surfaces. We have developed this novel method which has not been reported hitherto. The principal compound chosen for this study was ibuprofen due to its bitter taste and its common use among the paediatric population. The zinc oxide and titanium dioxide nanoparticles have been successfully adsorbed onto the surfaces of Ibuprofen particles. To assess potential of nanoparticles to mask taste, dissolution tests which simulated buccal cavity conditions were carried out. Additionally comparative dissolution studies of the ibuprofen particles coated with zinc oxide and titanium dioxide and marketed suspension was carried out at intestinal pH (7.2) to assess the drug release through the adsorbed nanoparticles onto the surface of ibuprofen. 2% Ibuprofen suspension was prepared in 500 ml beaker using a dispersion media containing 0.5% (w/w) PVP, 0.5% (w/w) HPMC and 0.1% (w/w) SLS and stirred using a hand stirrer to disperse lumps followed by magnetic stirring for 20 minutes. A variety of suspensions were made using different amount of 2% (w/v) TiO2 and ZnO 2%(w/v) nanosuspensions and Ibuprofen suspension to give final concentrations of 5%, 25% and 50% (v/v) followed by sonication for 15minutes.The Ibuprofen particles along with the adsorbed nanoparticles onto its surfaces were recovered by filtration using 0.22 µm filter paper and funnel. The powder was allowed to dry for 24 hours at room temperature. Energy dispersive x-ray spectroscopy (EDX) and scanning electron microscopy (SEM) images were collected to verify the adsorption. Quantification of drug in ibuprofen suspensions and powders with nanoparticles adsorbed to the drug surfaces was carried out by HPLC.

This data was then used to determine the concentration of nanoparticles that had adhered to the surface of ibuprofen. Dissolution tests were carried out on raw ibuprofen powder and powders containing ibuprofen with inert particles adsorbed on to the surface, all at strength of 100 mg of

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ibuprofen. SEM images (Figure 1 (B&D)) showed that inert nanoparticles adsorbed on to the surfaces of coarser ibuprofen particles which were confirmed by EDX (Figure 2 (Cand D)). It was observed the particle was heavily coated with zinc oxide compared to TiO2 which probably could be because of the higher free energy of zinc oxide .As the surface energy increases the more ordered mixing occurs.

Dissolution studies carried out at saliva pH (7.0) showed a slower dissolution rate when nanoparticles were adsorbed to ibuprofen compared to raw ibuprofen powder (Figure 2 (B)). Whereas no significant decrease in dissolution rate was observed for the ibuprofen particles with the adsorbed nanoparticles at intestinal pH (7.2) compared to the marketed suspension (Figure 2 (A)). This indicated that without affecting the dissolution rate at intestinal pH, nanoparticles served as a significant barrier between aqueous media and drug and therefore have the potential to be used in masking the unpleasant taste of some pharmacological agents.

Keywords: Taste masking, nanoparticles, zinc oxide, ibuprofen, Scanning electron microscopy

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UNIFORM PHARMACEUTICAL MICROPARTICLES WITH WELL-DEFINED PROPERTIES PRODUCED BY A NOVEL MICROFLUIDIC JET SPRAY DRYER

Winston Duo Wu, Xiao Dong Chen

School of Chemical and Environmental Engineering, College of Chemistry, Chemical Engineering and Materials Science, Soochow University, Suzhou, Jiangsu Province

Email: duo.wu@suda.edu.cn

A novel microfluidic jet spray dryer (MFJSD) has been utilized to fabricate uniform pharmaceutical microparticles with well-defined properties in a single step. This simple, waste-free and scalable synthesis process avoids use of organic solvents, prolonged chemical reactions and separation steps, ensuring close to 100% encapsulation of therapeutic agents and preventing wastage of expensive drugs.

In this paper, Eudragit RS 30D and three types of carbohydrates, i.e. lactose, glucose and sucrose are used as carriers with Vitamin B12 as model drug. The effects of precursor formulation and spray drying temperature have been precisely investigated upon microparticle size, morphology and structure. Well- controlled drug release profile has been consequently realized.

Keywords: Spray drying, uniform microparticles

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NOVEL ORAL SNEDDS OF ARTEMETHER: THE FUTURE CLINICAL OUTCOME

Gannu Praveen Kumar, Makula Sucharitha

1St. Peter’s Institute of Pharmaceutical Sciences, Vidyanagar, Hanamkonda Email: ghalo2010@gmail.com

Introduction

The eradication of malaria can be considered as a realistic approach since good surveillance and high intervention coverage between 2000 and 2007 has resulted in the reduction of malaria cases and deaths by 50% or more in many countries.The therapeutic efficacy of existing antimalarial drug artemether has the true potential to develop novel delivery systems and an attempt to identify challenges required to optimize malaria therapy for the benefit of human mankind is vry much essential. Traditionally, enhancing drug therapy has involved seeking of new chemical entities or incorporation of existing drugs into novel drug delivery systems.

Materials and Methods

The objective of the present investigation was to formulate novel oral self nanoemulsifying drug delivery systems (SNEDDS) using Labrafac as oil phase. SNEDDS based on polyethylene glycol and commercially available cationic surfactant was formulated and their application in improving the delivery of a lipophilic anti-malarial drug, Artemether was also evaluated. Artemether loaded SNEDDS were characterized with respect to mean globule size, SEM analysis, FTIR studies, DSC analysis, X-ray diffraction studies and in vitro drug release studies in comparison to the plain drug solution and marketed preparation.

Results and Discussion

Artemether SNEDDS showed excellent self emulsification efficiency and released >98% of the drug in just 15 min whereas the marketed preparation showed only 41% drug release at the end of 1 h. The mean globule size for optimized artemether SNEDDS was 117.9 nm. Comparative in vivo anti-malarial performance of the developed SNEDDS was evaluated with that of the marketed preparation in albino male mice infected with Plasmodium berghei. The parameters studied were percent parasitemia, activity against time and animal survival period. In vivo anti-malarial activity of artemether was enhanced when formulated as SNEDDS, in comparison to a conventional plain drug solution and with that of marketed formulation which are currently in use to treat malaria patients. The antimalarial studies revealed that artemether SNEDDS resulted in significant improvement in the anti-malarial activity (P<0.05) as compared to that of marketed preparation and artemether was solubilized in the oily phases and surfactant without any signs of crystallization. The developed SNEDDS highlights stability and safety for oral administration and its potential application in the treatment modality for the development of oral stable colloidal carriers.

Keywords: Artemether, Bioavailability, nanoemulsion, oral, antimalarial

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APPLICATION OF HIBISCUS ESCULENTUS (OKRA) GUM IN SUSTAINED RELEASE DOSAGE FORM OF PROPRANOLOL HYDROCHLORIDE

Nurul Dhania Zaharuddin, Mohamed Ibrahim Noordin, Ali Kadivar Department of Pharmacy, Faculty of Medicine, University of Malaya, 50603,

Kuala Lumpur, Malaysia Email: andee25@gmail.com

Okra gum which was extracted from the pods of Hibiscus esculentus was evaluated on its application as a natural binder in the development of a sustained release dosage form of an antihypertensive drug, Propranolol hydrochloride. Okra fruits were sliced and soaked immediately in distilled water to extract out the mucilage, precipitated using acetone and further dried in a desiccator. It is then grounded and sieved to produce Okra powder. Its physical characteristics such as solubility, pH, moisture content, viscosity, morphology using X-Ray Diffraction Analysis (XRD) and Field Emission Scanning Electron Microscope (FESEM) was studied. Thermal analysis was conducted using Differential Scanning Calorimetry (DSC) and its infrared spectrum had been developed using Fourier Transform Infra-red (FTIR). Okra gum powder were then used as a retarding polymer and sodium bicarbonate was used as effervescent agent to produce floating sustained release tablets of Propranolol hydrochloride tablets.

These sustained release tablets were developed to create a uniform drug therapy that is specifically released in the upper part of gastrointestinal tract. Its floating behavior, in-vitro drug release and swelling index were studied. The tensile strength was also evaluated by conducting hardness and friability tests. Dissolution profile studies for in-vitro drug release indicated that Okra Gum was able to control drug release by retarding its release in a moderate manner up to 24 hours. It also produced tablets with better hardness and lower friability, which shows an increase in the tablets’ tensile strength. Hence, Okra Gum was testified as an effective binder to produce favourable Propranolol hydrochloride sustained release tablets.

Keywords: Hibiscus esculentus, Okra gum, sustained release, tablet, Propranololhydrochloride

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FUTURE GREENER BIOPHARMACEUTICAL (NBP) TO CENTRAL NERVOUS SYSTEM (CNS): EFFECT OF POLY(D,L-LACTIC-CO-GLYCOLIC ACID) AND CHITOSAN MOLECULAR

WEIGHT ON FORMULATION.

Nur 'Izzati Mansor, Abd Almonem Doolanea, Nurul Hafizah Mohd Nor, Nurul Nabihah Mohamed Noor, Nur Syafiqah Feisal Hamdee, Abubakar Danjuma Abdullahi, Farahidah Mohamed,

International Islamic University Malaysia, Malaysia Email: nurizzatimansor@gmail.com

“Neurobionanoparticle” (NBP) was synthesized from two biodegradable polymers; Poly(D,L-lactic-co- glycolic acid) (PLGA) and chitosan and plant-origin material (Nigella sativa), intended for delivery of plasmid DNA to the central nervous system (CNS). Two independent variables were employed namely, molecular weights of hydrophilic PLGA 50:50 (14 kDa and 34 kDa) and chitosan (50-190 kDa and 190-310 kDa). Size, surface morphology, zeta potential, glass transition and in vitro transfection studies were characterized as a function of those multiple variables. The results suggested that fabrication of NBP using the diffusion-solvent-evaporation method employing PLGA and chitosan regardless of molecular weights successfully produced nanospherical particles with particle size of around 364 to 411 nm. It was observed that the particle size did not increase in the presence of serum, which indicates that the aggregation is not likely to happen. The loading of pDNA into PLGA/chitosan-Nigella sativa nanoparticles was confirmed as shown by electrophoretic mobility analysis. Zeta potential values of lyophilized NBPs were in the range of +42.6 ± 1 to +65 ± 2 mV depending on molecular weight of PLGA and chitosan (NBP3<NBP1<NBP2<NBP4 were found, respectively), which were much more positive compared to zeta potential of NBP before lyophilization, depending on molecular weight of PLGA and chitosan (NBP3<NBP1<NBP2<NBP4 were found, respectively). The recorded isoelectric point was in the range between 8 and 9 for all preparations. All formulations revealed higher Tg for PLGA than Tg for PLGA alone (anti-plasticizing effect). The molecular weight of the PLGA used obviously influenced the Tg of NBP fabricated. As the molecular weight reduced, the Tg of NBP reduced as observed. The interaction between chitosan and PLGA in the NBP formulations may contribute the anti-plasticizing effect. The higher Tg in NBP2 and NBP4 is due to higher molecular weight chitosan that seems to have more anti- plasticising effect on the same molecular weight of PLGA (NBP1 and NBP3 respectively). From in-vitro transfection studies, all NBP formulations exhibited a high level of pGL3 expression compared to the naked pDNA. These data showed that the functional integrity of PGL3 was also maintained in NBPs.

According to the results, we suggest pDNA-loaded PLGA/chitosan- Nigella sativa nanoparticles (NBP) have the potential to be used for in vivo studies.

Keywords: Neurobionanoparticle; Poly(D,L-lactic-co-glycolic acid); chitosan; Nigella sativa; plasmid DNA.

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Fig. 1: The SEM images (left) of NBP fabricated by using different molecular weight of PLGA in primary emulsion, (A) NBP1 and (B) NBP3; and Electrophoresis mobility analysis of pDNA-loaded nanospheres (right).

Fig. 2: Particle size distribution of NBPs suspended in deionized water (thin lines) and fetal bovine serum (thick lines).

Fig. 3: Comparison of zeta potentials (left); and effect of pH values on zeta potentials for all NBP formulations (right).

Fig. 4: Glass transition temperatures (left) and transfection of N2a with NBPs (right).

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FORMULATION DEVELOPMENT, EVALUATION AND ANTI-INFLAMMATORY EFFECTS OF KETOPROFEN CREAM ON RHEUMATOID ARTHRITIS PATIENTS

Saeed Ur Rashid Nazir, M. Razi Ullah Khan University Of Sargodha, Pakistan

Email: srnazir@yahoo.com

Purpose: Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) have their historical origin as the derivatives of plants, which were observed to have their therapeutic effects in disease conditions. Topical delivery of NSAID is most widely used in the treatment of pain disorder. Ketoprofen is widely used NSAID but cream formulation is not available in Pakistan. To develop topical cream formulation of Ketoprofen to avoid all the potential adverse effects occur with the use of oral dosage forms NSAID and also remain stable for longer period of time.

Methods: Ketoprofen cream was prepared and its anti-Inflammatory effects were evaluated in human subjects to determine its efficacy in reduction of pain, swelling and redness. This cream formulation was checked on a group of thirty volunteers and it was found that ketoprofen cream is highly effective to lower the pain and to remove swelling and redness in Rheumatoid Arthritis patients.

Accelerated Stability Study of Ketoprofen cream was done at three different temperatures, room temperature, 40°C and 60°C for a time period of 6 months. The remaining percentage of drug was determined by an assay on UV- Visible Spectrophotometer. It was found that the highest percentage of remaining drug concentration was obtained by the cream sample stored at room temperature (22±5°C). Other physical parameters such as visual appearance, pH, and tube extrudability were also evaluated for a period of 6 months.

Results: The cream formulation stored at Room temperature (22 ± 5°C) exhibited most satisfying results of all parameters as compared to storage at 40°C and 60°C. It is evident from the anti-inflammatory results that Ketoprofen cream is very effective to mimic the pain in Arthritis patients. This Study results reveals that Ketoprofen cream formulation causes a significant reduction in pain scales, removes the redness and swelling and improves the walking ability in Rheumatoid Arthritis patients.

Conclusion: By using Ketoprofen cream formulation can avoid all the potential adverse effects occur with use of oral dosage form NSAID in Rheumatoid Arthritis patients.

The cream formulation of Ketoprofen has no direct contact of active drug with stomach wall. This can be a good reason to eliminate the chances of gastric mucosal damage to a reasonable level that is caused by the use solid dosage forms of Ketoprofen.

Keywords: Ketoprofen, NSAID, Cream, Formulation, Rheumatoid Arthritis

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GREEN TECHNOLOGY EXTRACTION OF BIOACTIVE COMPOUNDS FROM ZINGIBERACEAE PLANTS USING SFE

Muhammad Nor Omar, Summaiya Razman, Nor Hazwani Mohd Hasali, Ahmad Muzammil Zuberdi Kulliyyah of Science, International Islamic University Malaysia, Malaysia

Email:mnoromar@iium.edu.my

Introduction: SFE employs the use of supercritical fluid especially CO2 as the extracting solvent replacing the use of conventional organic solvents. It is a green technology that has been widely used in the food, cosmetics and pharmaceuticals industries, as an alternative to conventional methods, i.e. solvent extraction and solid-phase microextraction (SPME).

Materials and Methods: The extracts of Zingiber puberulum, Zingiber spectabile and Kaempferia galanga were obtained using SFE at 48 Mpa and 40°C of extracting pressure and temperature respectively. The extracts were then analysed using gas chromatography-mass spectrometry (GC-MS) instrument.

Results: Several compounds were found in the SFE extract of Z. puberulum with fatty acids; i.e. palmitic acid (65.7%) and oleic acid (15.9%) were the major constituents and small percentages of various terpenic compounds. The sesquiterpene compounds identified in the SFE extract of Z. puberulum were α-bisabolol, β-elemene and caryophyllene while in Kaempferia galanga, the major compound extracted was ethyl p-methoxycinnamate.

Conclusion: It could be concluded that the important phytochemicals could be successfully extracted from Zingiberaceae family using SFE by optimizing the extracting conditions in order to ensure the optimum yield of the bioactive

Keywords: SFE, phytochemical constituents, Zingiber puberulum, Zingiber spectabile, Kaempferia galanga

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EXTRACTION SELECTIVITY-A NEW TOOL FOR GREEN PROCESS ANALYSIS AND DESIGN OF SOLID-LIQUID EXTRACTOR

Umar Isah Abubakar¹, Chua Lee Suan², Ramalan Aziz²

1Product and Process Development (PPD) Unit, Chemical Engineering Fundamentals Modelling and Simulation (ChEFMS) Research Group, Department of Chemical Engineering, Ahmadu Bello University,

Zaria, Nigeria; ²Institute of Bioproduct Development (IBD), Faculty of Chemical Engineering, Universiti Teknologi Malaysia, 81310 Skudai, Johor, Malaysia

Email: iaumar@ibd.utm.my

In process synthesis, design and optimization of solid-liquid extractors, extraction yield (EY) has been the only process parameter used for determining the process performance for centuries. However, since EY relates the product extract(s) to the whole amount of feed rather than the actual quantity of feed that disappeared in the extraction, it has some limitations. Among other serious shortcomings, EY cannot accurately give the real performance and clearly reveal the effects of process variables on the extraction. The normal plot of EY experimental data generally follows the exponential growth and steady stationary curves. Moreover, EY cannot be conveniently and efficiently used as a criterion for quick evaluation of process economic potentials in either the so-called solvent selective single or multiple extraction(s) prior to detailed profitability analysis and for minimization of undesired side extraction(s) that occur along with the desired extraction in multiple extraction(s). This paper introduces a concept of extraction selectivity (ES) as a new tool for process analysis in green solid-liquid extraction that overcomes the limitations of EY. It also demonstrates how overall ES of desired extract with respect to undesired extract(s) can provide more realistic response based on the effects of process variables in multiple extractions. New simple equations have been developed based on the concepts of multiple reactions and process engineering. Some of the equations are employed in the analysis of green solid- liquid extraction of andrographolide water extract and other water soluble phytochemical compounds from Andrographis paniculata as a case study and the results are shown in Fig. 1(a) to (c). It can be observed from the analysis of variance (ANOVA) for OYA and OSA as displayed in Table 1 that OSA is more sensitive to variation of process variables than OYA. The profiles of the overall ES of desired extract with respect to undesired extract(s) have the capability of debunking the plots of EY and depicting the true feasible regions for profitable operation. With amazing abilities to overcome the limitations of EY, the new concept of ESs can be a powerful criterion in predicting profits, choosing extractors and extraction schemes that will maximize the extraction of desired extract while minimizing the unwanted extracts at the early stage of product and process development.

Keywords: Extraction yield (EY); Extraction selectivity (ES); Multiple extractions; Green product and process development; Andrographolide water extract; Andrographis paniculata

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Figure 1. Effect of particle size and time on (a) overall yield of andrographolide, (b) overall selectivity of andrographolide, (c) overall selectivity of other phytochemical compounds (OSOPCC) and (d) overall selectivity of andrographolide with respect toother phytochemical compounds water extracts for S-L ratio 1g:50 mL at 80 C

Table 1. Analysis of variance (ANOVA) for the selected factorial models of OYA (%) and OSA (%)

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GREEN PROCESS DEVELOPMENT OF HERBAL AND/UPSTREAM PHYTOCHEMICAL PRODUCTS IN DRUG DISCOVERY AND DEVELOPMENT

Umar Isah Abubakar¹, Ibrahim Ali Mohammed-Dabo², Idris Muhammad Bugaje³,Hadiza Nuhu⁴

1Product and Process Development (PPD) Unit, Chemical Engineering Fundamentals Modelling and Simulation (ChEFMS) Research Group, Zaria, Nigeria; ²Petroleum and Renewable Energy Research Group, Department of Chemical Engineering, Ahmadu Bello University, Faculty of Engineering; ³Office of the Director General, National Research Institute for Chemical Technology (NARICT), Federal Ministry of Science and Technology, Zaria, Nigeria; ⁴Department of Pharmacognosy & Drug Development, Ahmadu

Bello University, Ahmadu Bello University, Faculty of Pharmacy, Zaria, Nigeria Email: iaumar@ibd.utm.my

Herbal, phytochemical, biopharmaceutical and related products are produced in batch or/and semi- batch mode. This differs from commodity products that are obtained in large quantities from chemical, petroleum and petrochemical industries, which operate in continuous mode, as intermediates to other manufacturing firms. Batch and semi-batch processes are always dynamic in nature, and that creates additional challenges in their product and process design, scheduling and optimization. These processes are best described with batch process simulators that can handle sequencing of events and process dynamics. This paper describes how green process of herbal and/or upstream phytochemical products can be produced with aid of production scheduling tools and batch process simulators of SuperPro Designer®. It examines green process development of a pilot plant for the production of anti-malarial powdered extract from raw Herb 25 (NAFDAC Reg. No: NRN-A7-0155L) as a case study. The procedure and detailed steps are illustrated in Figs. 1.0 to 4.0, while the results for design and analysis are presented in Tables 1 and 2 and Figs. 5 to 7. This technique can be used to speed up drug discovery and development cycle for any potential candidate and for profitable manufacturing.

Keywords: Green process development; Process design; Process scheduling; Process optimization; Batch process simulator; Powdered extract

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Fig. 1: Process Design Procedure Fig. 2 : Preliminary Database Creation Step

Fig. 3: Design and Analysis Step Fig. 4: Process Simulation Step

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Table 1. Process Scheduling for the Base Case Model

Table 2. Comparative Analysis of the Base Case, Schemes I and II Process Models

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Fig. 1: Process Flow Diagram (PFD) for Base Case Process Model

Fig. 2: Process Flow Diagram (PFD) for Scheme I Process Model

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Fig. 3: Process Flow Diagram (PFD) for Scheme II Process Model

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1H NMR AND UV/ VISIBLE SPECTROPHOTOMETERIC STUDY OF THE ARSENIC COMPOUNDS WITH GLUTATHIONE IN BLOOD AND AQUEOUS SOLUTION A

TOXICOLOGICAL AND PHARMACOLOGICAL PERSPECTIVE.

Muhammad Farid Khan

Gomal University Dera Ismail Khan, Pakistan Email: drfarid_2006@yahoo.com

Metallo elements have both toxic and pharmacological effects on plants and animals including humans and is always a public health issue of major concern. Arsenic (AS) is environmentally wide spread toxicant causing vascular diseases, skin diseases nephropathy and cancer. We have examined the effects of Arsenic salt on glutathione (GSH), an oxidant in blood components and aqueous solution and suggested mechanisms of action of Arsenic using spectroscopic technology including UV-visible and proton nuclear magnetic resonance spectroscopy. Different mechanisms have been suggested for the action of Arsenic (AS) as a model of in vivo reaction.

Keywords: Glutathione (GHS), Thiolates anions, Arsenic, compounds, UV/visible spectrophotometric and 1H Nuclear Magnetic Resonance Methods

38

STRUCTURAL MODIFICATION OF A NATURAL POLYMER CASSIA TORA BY MICROWAVE ASSISTED GRAFTING TECHNIQUE INTENDED TO USE SUSTAINED

RELEASE MATRIX TABLET FORMULATION

Shubhasis Dan, Tapan Kumar Pal

Department Of Pharmaceutical Technology, Jadavpur University, India Email: sdan@research.jdvu.ac.in

Recently the use of natural gums and polymers are increasing many folds by the pharmaceutical industries as a rate controlling exipient in case of sustained release formulations significantly. Natural gums and polymers have many advantages over synthetic materials like biodegradability, biocompatibility, better patient tolerance, low cost, easy availability, edible source and non toxicity. But these natural gums also have some drawbacks- they under goes uncontrolled hydration, microbial contamination variation of viscosity during storage etc.

Therefore need to modify the natural polymers are justified and can be used as a successor of the conventional synthetic polymers.

In the present study microwave assisted grafting technique is used to modify Cassia tora (CT) [Caesalpinaceae plant family and genus Cassia] which is a commonly used natural polymer, derived from the seeds of Cassia tora Linn, herbaceous annual weed occurring throughout India. This microwave assisted grafting method offers microwave method offers many advantages such as— a) Short reaction times, b) Dry or aqueous working conditions, c) Fast and homogeneous heating, d) High-temperature chemistry with modified selectivities.

Here Acrylamide (AM) and Cerric ammonium nitrate (CAN) was chosen as a grafting material and initiator respectively. Acrylamide -grafted-Cassia tora was prepared by free radical induced polymerization method assisted by microwave radiation. In 100 ml water 1 gm CT was taken and dispersion was prepared by overnight stirring. In 30ml water acrylamide was dissolved and the solution was mixed with CT dispersion followed by 1hr stirring. Approximately 300 mg of CAN was taken and dissolved in 30ml water and added slowly to the dispersion with continuous stirring. The final mixing was then irradiated by microwave with a 3 minute heating-cooling cycle. The same was done with the other batches also. The percentage grafting efficiency (%GE) and grafting percentage (%G) was calculated using the equation 1 and 2.

Six different bathes having code names F1, F2, F3, F4, F5 and F6 was prepared with a variation in the amount of acrylamamide (10, 7.5, 2.5, 5, 9 and 8 gm respectively). The amount of CT and CAN was fixed at 1 gm and 300 mg respectively. The percentage grafting efficiency (%GE) was found as 16.15%, 62.64%, 72.19%, 94.95%, 37.39% and 1.49% whereas percentage grafting (%G) was 161.62%, 470.14%, 181.2%, 476.1%, 336.7% and 11.96 respectively.

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As per the “Organization of Economic Co-operation and Development (OECD) guideline for the test of chemicals” acute oral toxicity study of the grafted CT was performed on five swiss albino female mice.

The mortality rate was observed by visible observation. There was no death. So therefore, as per the globally harmonized system (GHS) if LD50 value is greater than the 2000 mg/kg dose then the test product will be fallen under the “Category 5” and toxicity rating will be “zero”. So, acrylamide grafted Cassia tora is under the “category 5” as well as toxicity rating is “zero”.

Keywords: Cassia tora, acrylamide, grafting, microwave, CAN

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DOCKING STUDIES OF AEGLE MARMELOS PLANT COMPOUNDS AGAINST GASTRIC CANCER CELL SURFACE RECEPTOR PROTEINS – CD340 AND FGFR2B

Rekha Govindan¹, Sumi Rana¹, Rahul Kumar¹, Manivannan Sethuraman²

1Aarupadai Veedu Institute of Technology, India; ²Transstellar Journal Publications and Research Consultancy Private Limited (TJPRC), India

Email: rekhagovindan2000@yahoo.com

A number of natural products, with diverse chemical structures have been isolated as anticancer agents.

Several potential lead molecules have been isolated from plant sources and many of them have been modified to yield better analogues for anticancer activities. Search is still continued for new effective lead molecules for manufacturing cancer drugs as the disease continues to be still unconquered by the man. Aegle marmelos (L.) Corr., belongs to the family Rutaceae and is locally known as Bael tree. The unripe or half ripe fruit is considered as astringent, digestive and stomachic and used for treating diarrhoea and dysentery. The fresh juice of bael leaves along with honey is used as a laxative and febrifuge. It is reported effective against asthmatic complaints. The phytochemical analysis of the ethanolic extract of A. marmelos leaves revealed the presence of carbohydrates, tannins, flavonoids, alkaloids, betacyanins, quinones, phenols, coumarins, glycosides and steroids. HPLC analysis showed the presence of rutin, ursolic acid, quercitin and marmesin.

Gastric cancer is the fourth most commonly diagnosed cancer world-wide. The search of potential drug targets against gastric cancers is actively going within the global research community. The present study of in-silico structure based drug designing was carried out for finding ligand compounds from A.

marmelos for two major receptor proteins, namely CD340 and FGFR2b that highly expressed on Gastric cancer cell surfaces. The methodology involves the use of virtual tools, Dukes ethanobotany- phytochemical and ethanobotanical databases to obtain the compounds available in the tree A.

marmelos, ISIS Draw to obtain the chemical structure of ligands, Protein DataBase to obtain the proteins present on the surface of gastric cancer cells with the PDB id, selection of two major receptors namely CD340 and FGFR2b, analysis of secondary structures of CD340 and FGFR2b by Ramachandran plot.

Protein separation was done using WHAT software where the protein is repaired followed by conversion into mol2 format using TSAR software. Each protein and each ligand were docked using GOLD software.

The parameters used were minimum number of operations on run 10000 and maximum number of operations runs 25000. The compounds which scored best were confirmed with other docking software such as Molegro and Ehits. The highest score generated compound was determined as the best lead compound against gastric cancers that can be targeted for therapeutic properties.

Keywords: Aegle marmelos plant compounds, Gastric cancer cell surface receptor proteins, Docking studies

41

DESIGN AND SYNTHESIS OF NOVEL FLAVONOIDS AS GABAA RECEPTOR LIGANDS

Aditi Kaushik¹, Manish Kaushik², Vinay Lather²

1Punjab Technical University, Jalandar, Panjab, India; ²JCD College of Pharmacy, Sirsa, Haryana, India Email: aditikaushik2006@gmail.com

Mental disorders are recognized as significant changes in behavioral or psychological patterns. The drugs treating mental disorders are employed on the basis of the neurotransmission in Central Nervous System (CNS), which plays very important in the psychiatric disorders. Thus, pharmacological knowledge GABAA receptor helps to design the new and potent ligands for the receptor¹. This led to the development of compounds more selective for various subunit combinations constitute the benzodiazepines binding site in GABAA receptor complex². Thus, with the advancement in the field of drug development for GABAA receptor, the designing of more target specific CNS active agents with fewer side effects become possible known as non-benzodiazepines. In this area, drugs leads of natural sources have been identified as important candidate³. Flavonoids family provides important lead for the development of new potent and selective ligands for the GABAA receptor as compared to other lead molecules.

Flavonoids are generally describing a broad collection of natural products that includes C6-C3-C6 carbon framework. As partial agonists they possess fewer side effects such as sedation, myorelaxation etc⁴. QSAR models were generated which were validated on Flavone derivatives. Moreover, new flavone derivatives were synthesized on the basis of generated QSAR models and characterized⁵. Future research focuses on the selection of more potent and selective substituents as Flavones derivatives.

Keywords: GABAA receptor, Flavonoids, QSAR models

Figure 1. General Structure of Flavone Family

1

1. Bloom, F.E. Neurotransmission and the Central Nervous System. Joel G.Hardman, Lee E. Limbard.In The Pharmacological Basis of Therapeutics, 9th edition; Gilman, A.G., Goodman, L.S., Rall, T.W., Murad, F., Eds.; Macmillan Publishing Co.: New York, 1985; pp 304-314Reddy, M.V.;Chandrasekhar,

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4. Wang, F.; Shing, M.; Huen, Y.; Tsang, S.Y.; Xue, H. Neuroactive flavonoids interacting with GABAA receptor complex. Curr Drug Targets CNS Neurol Disord. 2005, 4(5), 575-585.

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PREPARATION, CHARACTERIZATION AND REDUCTION OF BURST RELEASE OF BSA FROM BIODEGRADABLE PLGA MICROSPHERES

Mohd Mokhlesur Rahman¹, Rezaul Haque Ansary¹, Farahidah Mohamed¹, Mohamed bin Awang², Kamaruzzaman bin Yunus^1<