Volume 4

April-June 2012


The concept of QbD was mentioned in the ICH Q8 guidance (3), which states that “quality cannot be tested into
products, i.e., quality should be built in by design”.

Review Articles

U Ashok Kumar, C Manjunath, T Thaminzhmani, Y Ravi Kiran, Y Brahmaiah

Certain medicinal plants are believed to promote positive health and maintain organic resistance against infection by re-establishing body equilibrium and conditioning the body tissues. It is tempting to speculate that the restorative and rejuvenating power of these herbal remedies might be due to their action on the immune system and some of the medicinal plants are believed to enhance the natural resistance of the body to infections. Plant derived materials (proteins, lections, polysaccharides, etc.) have been shown to stimulate the immune system. Ayurveda and other Indian literature mention the use of plants in treatment of various human ailments. Some of the plants with established immunomodulatory activity are Viscum album, Panax ginseng, Asparagus racemosus, Azadirachta indica, Tinospora cordifolia, Polygala senega, Ocimum santum, Withania somnifera among others. There are a number of plants that have been reported to have immunomodulatory activity. The present paper review plants which have shown experimental and clinical immunomodulatory activity.

Keywords: Immunomodulatory Activity, Sheep Red Blood Cells (SRBC), Cyclophosphamide, Pyrogallol, Heamagglutination Antibody (HA) Titer, Delayed Type Hypersensitivity (DTH), Neutrophil Adhesion Test, Carbon Clearance.

Research Articles

Shwetha K, Swamy N G N

The aim of this work was to synthesize semi-Interpenetrating Polymer Network superporous hydrogels of hydroxypropyl guar and chitosan, by cross-linking chitosan with glyoxal and to study its swelling behavior for application as a gastroretentive drug delivery system. Chitosan- hydroxypropyl guar superporous hydrogels of metoprolol tartrate were synthesized by gas blowing method. The effect of pH on the swelling ratio was determined. Swelling reversibility studies were also carried out. Fourier transform infrared spectroscopy analysis and scanning electron microscopy studies were undertaken to characterize the drug loaded super porous hydrogels, while dissolution studies were carried out to assess release characteristics. Swelling was highly dependent on the extent of crosslinking and the amount of the polymer present in formulation. The higher the amount of cross-linking agent, lower was the swelling ratio. The superporous hydrogels were highly sensitive to pH of swelling medium, and showed reversible swelling and de-swelling behaviour while still retaining their mechanical stability. Apparent density was dependent on the volume of the superporous hydrogels and decreased with increasing crosslink density. Degradation kinetics showed that chitosan superporous hydrogels had good water retention capability. Drug release was inversely related to the amount of cross-linking agent. The studies revealed that chitosan- hydroxypropyl guar superporous hydrogels can be used as a gastroretentive drug delivery system in view of their swelling characteristics in acidic pH.

Keywords: Gastro-retentive Drug Delivery, Superporous Hydrogels, Chitosan, Hydroxypropyl Guar, Metoprolol Tartrate, Swelling Ratio.

C N Okwuosa, D C Nwachukwu, Nkiru Azubuike

The antiulcer activity of chloroform leaf extract of Aspilia africana on necrotizing agent induced gastric ulcer and its effect on gastric motility were investigated using male albino Wistar rats. Phytochemical analysis of the extract revealed the presence alkaloids, flavonoids, saponins, steroids, terprenoid, proteins and tannins. Acute toxicity test showed an oral LD50 greater than 5000mg/Kg. The Animals were divided into four groups (A-D); groups A and B were given 250 and 500mg/Kg of the extract respectively, group C was given 200µg/Kg of misoprostol (positive control) while group D was given 5ml/Kg of 3% Tween 80 (negative control). Results showed that the different doses of the extract significantly protected the stomach from ulceration caused by necrotizing agent in a dose-dependent manner. The mean ulcer indices of groups A and B were 3.32 ± 1.52 and 2.90 ± 0.42 respectively while that of group C was 1.64 ±0.25. These values were all significant (p< 0.05, p<0.01) when compared that of group D (8.94± 1.10). Percentage ulcer inhibition of the misoprostol was higher than that of the extract. Gastrointestinal motility studies showed that the extract significantly inhibited motility but was not potent as atropine, whose percentage inhibition of motility twice that of the extract. Thus, Chloroform extract of Aspilia africana, demonstrated strong protection against gastric ulcer and moderate inhibition of gastrointestinal motility.

Keywords: Aspilia africana, Ulcer, Necrotizing Agent, Gastrointestinal Motility, Misoprostol, Atropine, Phytochemical Analysis, Acute Toxicity.

Hitendra S Mahajan, Ghanashyam A Girnar, Pankaj P Nerkar

The objective of the present study was to formulate surface solid dispersions (SSD) of gliclazide to improve the aqueous solubility and dissolution rate. Gliclazide is a BCS Class II drug having low aqueous solubility and therefore low oral bioavailability. In the present study, SSDs of gliclazide with two different carriers in different drug–carrier ratios were prepared by a spray drying method. Surface solid dispersions were characterized by differential scanning calorimetry (DSC), X-ray diffractometry (XRD), scanning electron microscopy (SEM), and Fourier transform infrared spectroscopy (IR) and evaluated for in vitro dissolution, and relative bioavailability studies using rabbit models. Spray drying resulted in stable and uniformly sized spherical particles of SSDs in comparison to probe sonication as revealed from SEM study. DSC and XRD study demonstrated that there was a significant decrease in crystallinity of pure drug present in surface solid dispersions, which resulted in an increased dissolution rate of gliclazide. Surface solid dispersions showed increase in relative bioavailability than the plain gliclazide suspension. The spray drying would be suitable method for dissolution and bioavailability enhancement of gliclazide.

Keywords: Spray Drying, Gliclazide, Surface Solid Dispersion, Dissolution, Bioavailability.

Awofisayo S O, Itina I I, Uwanta E J, Fabian U J

The study compared the disintegration and dissolution time of the antipsychotic drug, chlorpromazine hydrochloride (CPZH) tablet in the presence of simulated intestinal fluid (SIF), Simulated Gastric Fluid (SGF) and food modified SIF and SGF. Various quality control parameters including weight uniformity, tablet hardness, disintegration, friability and assay were assessed. SGF and SIF were employed as disintegration and dissolution media and compared with a food (1.3 ml full cream unsweetened evaporated milk, 2.67mg soluble starch) modified SIF and SGF (FMSIF and FMSGF) at 37 ± 0.5°C. The product assessed complied with the official specification for uniformity of weight friability and assay. The disintegration test showed significantly higher disintegration time for SIF and SGF (3.7 and 6.5 min) compared to the FMSIF and FMSGF (2.9 and 4.9s) (p< 0.05) but a significantly lower percentage drug release at 45 min in the SIF and SGF (52% and 43%) than the FMSIF and FMSGF (52% and 60%) (P< 0.05). The dosing condition of CPZH tablet should preferably be after meals to optimize drug release and subsequent absorption.

Keywords: Chlorpromazine, Modified SGF, Modified SIF.

Md Raihan Sarkar, A S M Monjur-Al-Hossain, Md Saiful Islam, A B M Faroque

Physical mixtures (PMs) of atorvastatin and four different hydrophilic swellable polymers (pregelatinized starch, hydroxypropyl methyl cellulose, poloxamer 407 and sodium carboxy methyl cellulose) were prepared at 1:0.5, 1:1 and 1:2 ratios. In vitro dissolution study was performed in distilled water for 60 minutes at 50 rpm and 37±0.5°C. Faster dissolution was achieved using poloxamer at 1:2 ratios; it was 87% after first 10 minutes of dissolution. However, considering complete dissolution for 60 minutes, atorvastatin release was increased in the following order: pregelatinized starch > poloxamer 407 > hydroxypropyl methyl cellulose > sodium carboxy methyl cellulose. In case of all the batches, statistically significant correlation between % release and polymer concentration was observed (P ˂ 0.5, ANOVA single factor). Mean dissolution time (MDT), time for 25% release (t25), 50% release (t50) and 75% release (t75) were also calculated. Significant correlation was found between polymer concentration and corresponding mean dissolution time values (P˂ 0.5, ANOVA single factor). Highest MDT was 13.85 minute for pregelatinized starch and lowest MDT was 0.5 minute for poloxamer. Release data were fitted in different model and release was found to be fitted best in Korsmeyer-peppas model where fickian diffusion mechanism was predominant.

Keywords: Atorvastatin, Physical Mixing Technique, Hydrophilic Swellable Polymer, Fickian Diffusion.

Minky Mukhija, Rohit Goyal, Ajudhia N Kalia

The study was designed to investigate anti-inflammatory active fraction(s) from the aqueous extract of Zanthoxylum alatum stem bark in acute and chronic models of inflammation. Wistar rats of either sex were employed. Acute inflammation was induced by subplantar administration of carrageenan (1 %) in rat hind paw. Chronic inflammation was induced by interscapular implantation of a sterile cotton pellet (50 mg). Alkaloid fraction (100 mg/kg b.w) was found to be more effective in comparision to flavonoid (100 mg/kg) in carrageenan induced inflammation model. Hence was selected for further detailed study. Pretreatment with alkaloid fraction (100, 150 mg/kg) have shown significant (p < 0.05) check on carrageenan induced paw edema and significantly (p < 0.05) decreased granuloma tissue formation, as compared to control. The alkaloid constituents are more potent in prevention of acute and chronic inflammation. Hence, the present study has concluded that the alkaloids fraction is responsible for its anti inflammatory claim.

Keywords: Zanthoxylum alatum, Rutaceae, Inflammation, Alkaloids, Flavonoids.

Jakia Sultana, Mohammad Salim Hossain, Muhammad Shahdaat Bin Sayeed, S M Ashraful Islam, Mohammad Safiqul Islam

Controlled release matrix tablets of Ciprofloxacin HCl were prepared and evaluated as the function of varying the concentrations of polymers e.g., Povidone K-30 and excepients e.g, Avicel pH 101. The concentrations were varied to investigate whether these variations can cause any change in release of Ciprofloxacin HCl molecule. Tablets were prepared by direct compression method. The granules were evaluated for drug content and drug excipient interaction. The tablets were subjected to thickness, diameter, hardness and in vitro release studies. The USP Basket method was selected to perform the dissolution test carried out in 1000 ml 0.1 N HCl for 8 hours with 50 rpm, at 37±0.5°C.The release rate was quantitatively determined by a UV-spectrophotometeric method. By comparing the dissolution profiles, it is revealed that significant differences were found among the drug release profile from different formulations matrices. From the study it is found that, Povidone K-30 based matrix tablets release greater percentage of active drug with incorporating the increasing amount of Avicel pH 101. The release of active drug from the prepared matrix tablet appears to follow the Higuchi kinetics model. Kinetic modeling of in vitro dissolution profiles revealed the drug release mechanism was diffusion controlled or Fickian transport which was only dependent on the type and amount of polymer used. The drug release followed both diffusion and erosion in all cases.

Keywords: Matrix Tablets, Ciprofloxacin HCl, Povidone K-30, Avicel pH 101.

M Karthik Raja, Ramu, Eswarama, C Anusha

Microencapsulation is a process by which very tiny droplets or particles of liquid or solid material are surrounded or coated with a continuous film of polymeric material. It means of converting liquids to solids, of altering colloidal and surface properties. The capsule protects the active ingredient from its surrounding environment until an appropriate time and material escapes through the capsule wall either by rupture, dissolution, melting or diffusion. In the view of converting the active pharmaceutical ingredients into dosage forms suitable for administration, the present study is an attempt to formulate a hydrogel bead of micron size by ionotrophic gelation technique using potato starch as a release retardant and thereby increasing the release time of the encapsulated drug and providing a delayed/controlled release formulation. It was observed that increase in polymer concentration, the drug release and particle size was gradually decreased. The formulation were investigated for various parameters life particle size, micrometric properties, surface morphology by SEM, incorporate efficiency and in vitro release study. With the obtained results of mentioned parameter it reveals that microbeads with high potato starch concentration (F1 & F2) show delayed release of aceclofenac. Decrease in concentration of alginate results in reduced size of the microbeads along with high efficiency, thus satisfied the need of formulation of delayed release aceclofenac microbeads.

Keywords: Microencapsulation, Aceclofenac, Potato Starch, Alginates, SEM.


Kamal Sachdeva, Preeti Garg, Manmohan Singhal, Birendra Srivastava

The present study provides the pharmacological evaluation of stem bark extract of Jatropha curcas L. for anti-diarrhoeal activity in rats. We made an attempt to study the effect of stem bark extract of Jatropha curcas L. on diarrhoeal disease. The different activities studied were castor oil-induced diarrhoea, magnesium sulphate induced diarrhoea and charcoal meal transit test. The result of the study reflected that methanol extract of the stem bark (100, 300 mg/kg) decreased total no. of faeces, wet faeces and distance travelled by charcoal plug and showed the antidiarrhoeal activity. Jatropha curcas L. extract demonstrates the anti-diarrhoeal activity in rats.

Keywords: Castor Oil-induced Diarrhoea, Charcoal Meal Transit Test, Diarrhoeal, Jatropha curcas, Magnesium Sulphate Induced Diarrhea.

Haresh Chaudhary, B N Patel, D M Patel, C N Patel

The present investigation describes the influence of the high substituted hydroxypropyl cellulose (HPC-H) and guar gum on release behavior and kinetics of theophylline sustained release tablets using 32 full factorial design. The amounts of Guar Gum (X1) and HPC-H (X2) were selected as an independent variables and drug release at 1hr (Q1) and at 8hr (Q8) and time required for 50% drug release (T50%) were selected as a dependent variable. Theophylline tablets were prepared by direct compression method using HPC-H with Guar Gum as release retardant in different proportions and MCC as directly compressible filler-binder. The parameter optimized using 32 factorial designs. The tablets of all batches were evaluated for various evaluation parameters. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. Regression analysis and response surface analysis were performed for dependent variables. The FTIR study was carried out for drug excipient compatibility Studies. The initial release was sufficiently higher in all formulations thus ruling out the need to incorporate a specific loading dose. Thus, the use of suitable polymer combinations that could provide initial higher release and release extension up to 12 hr. It was observed that type and ratio of polymer had significant influence on Q8, without significant influence on Q1 and T50%. Mathematical treatment of the in vitro drug release data suggests that, the drug release of all the formulations followed Korsmeyer-peppas model, the release exponent n<0.5 indicate that drug diffuses through the polymeric matrix by a Fickian (case I) diffusion mechanism. 

Keywords: 32 Full Factorial Design, Release Kinetics, Sustained Release, Response Surface Plot.

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