DISSOLUTION ENHANCEMENT OF SEROQUEL BY SOLID DISPERSION TECHNIQUES

ABSTRACTObjective: Seroquel is an antipsychotic drug with plasma half-life of 6 hrs and poor oral bioavailability (9%) due to extensive first-passmetabolism. A present work is an attempt to improve oral bioavailability of seroquel by solid dispersions (SDs) (to improve the aqueoussolubility and dissolution rate) so as to facilitate faster onset of action. Seroquel is a biopharmaceutical classification system Class II drug havinglow solubility (1.28 µg/ml).Methods: In the present investigation, an attempt was made to prepare SD with water-soluble carriers like polyethylene glycol (PEG 6000) PEG 6000and PEG 4000. The SDs were prepared by melting method and physical mixing method by using PEG 6000 and PEG 4000 in the ratio 1:1, 1:3 and1:5 respectfully. The prepared dispersions were evaluated for their physicochemical and dissolution characteristics. All the dispersions were easy toprepare, and the powder mass obtained in various formulations were free flowing under dry conditions. Physicochemical properties of the productswere characterized by Fourier infrared spectroscopy which reveals that there is no interaction between drug and polymer. In vitro dissolutionprofiles of Seroquel formulations of physical mixtures (PMs) and melting methods were studied using Lab India Disso 2000 dissolution apparatusemploying paddle method. 500 ml of 6.2 phosphate buffer was used as dissolution medium maintained at 37±0.50°C, and the stirrer rotation waskept at 50 rpm. Aliquots were withdrawn at different time intervals and measured for the absorbance for Seroquel at 244 nm using ultra violet-visiblespectrophotometer with a reference to suitably constructed standard plot.Results and Discussions: Mixture of drug:PEG 6000 in (1:3) ratio prepared by melting method gives the highest drug release (93.55%) than PM(88.12%) and pure drug (39.75%) in 60 minutes. The dissolution of all the preparation follows Higuchi order kinetics.Conclusion: It is concluded that in melting method, due to the fineness, amorphous state of the drug, particle size reduction and absence of aggregation,dissolution rate increases but in PMs only a marginal increase in dissolution rate because the size reduction process is not effective.Keywords: Dissolution, Solid dispersion, Seroquel

STABILITY OF FLOATING MICROSPHERES AT NORMAL AND ACCELERATED CONDITIONS

Objective: To study the stability profile of floating microspheres of repaglinide as per ICH guidelines under normal (25±2°C/60±5% RH) and accelerated condition (40±2°C/75±5% RH and 5-8°C/65±5% RH) for a period of six mo.Methods: Floating microspheres were prepared using ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMC) and subjected to stability studies. Physical appearance, scanning electron microscopy (SEM), % buoyancy, % residual drug content and drug release of stored formulation were evaluated after every two mo.Results: Change in color, size, and residual drug content showed no significant variations in formulations stored at a different set of conditions. SEM images showed no morphological transformation during the study. Less than 5% change was observed in buoyancy and drug release.Conclusion: The data depict that the formulation is sufficiently rugged for marketing worldwide under various climatic conditions including normal, oven and freezing temperature.Keywords: Stability, Microspheres, Buoyancy, Physical, Freezin

PREPARATION AND EVALUATION OF CONTROLLED RELEASE FLOATING MICROSPHERES OF REPAGLINIDE: OPTIMIZATION AND IN-VITRO STUDIES

ABSTRACTObjective: To develop and evaluate floating microspheres of repaglinide (RG).Materials and Methods: RG loaded noneffervescent microspheres of different ratios of ethylcellulose (EC) and hydroxypropyl methylcellulose (HPMCK4M) were prepared using polyvinyl alcohol as emulsifier by solvent evaporation technique. Various process variables such as polymer ratio, stirringspeed, concentration of drug, and emulsifying agent were studied. Compatibility of drug and polymers was studied by Fourier-transform infraredspectroscopy (FTIR). Characterization, in-vitro evaluation, and kinetic studies were performed.Results: FTIR spectra have revealed no drug-excipient incompatibility. The average particle size of microspheres was in the range of 312-359 μm. Theresults showed that floating microspheres were successfully prepared with good yield (56.15-64.3%), high entrapment efficiency (58.22-70.14%),and good floating behavior (63.1-76.2%), respectively. In-vitro release data indicates appreciable amount of drug is released (62.28-73.27%) from themicrospheres in gastric fluid. The mechanism of drug release founds to follow first order kinetics (r2=0.986).Conclusion: The developed floating microspheres of RG may be used for prolonged drug release for at least 12 hrs, thereby improving bioavailabilityand patient compliance.Keywords: Repaglinide, Compatibility, Kinetic, Ethylcellulose

ETHYLCELLULOSE FLOATING MICROSPHERES OF ANTIDIABETIC AGENT: IN VITRO AND IN VIVO EVALUATION

Objective: To develop and evaluate floating type gastro-retentive dosage form, appropriate for controlled release of repaglinide (RG) having a narrow therapeutic window.Methods: Repaglinide loaded microspheres (MS) using biological macromolecule ethylcellulose (EC) was prepared by a solvent diffusion-evaporation technique using polyvinyl alcohol (PVA) emulsifier. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). During formulation, various process optimisation parameters studied were stirring speed, the concentration of drug, polymer and emulsifier. Characterization and in vitro evaluation was performed. In vivo antidiabetic activity was performed on alloxan induced diabetic rats followed by histopathological screening.Results: The average particle size was in the range of 174-243 µm. Yield, entrapment and buoyancy of microspheres were 68.4­­-79.8, 58.6-73.1 and 71.8-84.1% respectively. 65.1% release of drug from optimised formulation was obtained which follows first-order kinetics (r2 = 0.989). Optimised formulation treated group shows significant (p<0.01) decrease in glucose level of blood as compared to pure drug treated group during the later hours of study with satisfactory results of histology.Conclusion: The investigation revealed the promising potential of gastro retentive microspheres for delivering RG for the treatment of non-insulin dependent diabetes mellitus (NIDDM)

WOUND HEALING ACTIVITY OF BARRINGTONIA ACUTANGULA FRUIT EXTRACT

ABSTRACTObjective: To evaluate wound healing activity of methanolic extract of Barringtonia acutangula fruits (MEBA).Methods: Both excision and incision models were used in rats. In the excision wound model, the wound area of each animal was measured on days0, 2, 4, 6, 8, 10, 12, and 14 after inflicting the wound. Wound contraction (WC) was calculated as a percentage change in the initial wound size. Thehistopathology study of the skin (newly formed on the wounds) was carried out on the 12 post wounding day. In the incision wound model, thetensile strength was measured using tensiometer on the 14th post wounding day.thResults: MEBA at 20% w/w showed highly significant wound healing activity (p<0.01) as compared to control. The percentage of WC on the 14 dayby MEBA at 5%, 10%, and 20% w/w were found to be 93.86%, 93.86%, and 96.43%, respectively. There is increased the number of fibroblasts,increased collagen tissue and complete epithelialization in the case of MEBA ointment 20% w/w.Conclusion: MEBA fruit (ointment) showed significant wound healing activity in both excised wound model (20% w/w) and incision wound model(10% w/w) rats.Keywords: Barringtonia, Wound healing, Excision, Incision.t

ANTIBACTERIAL AND ANTIOXIDANT ACTIVITIES OF METHANOLIC EXTRACT OF BAUHINIA RACEMOSA

Objective: To evaluate antimicrobial and in vitro [s1] antioxidant activities of methanolic extract of Bauhinia racemosa leaf.Methods: The antimicrobial activity was determined by the agar-well diffusion method. The antioxidant potential was evaluated by using various in vitro [s2] methods such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2, 2-azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS), phospho molybdenum reduction assay and ferric (Fe 3+) reducing power assays.Results: The maximum inhibition zone (26 mm) was found against Proteus mirabilis while lowest inhibition zone (20 mm) was observed against Acinetobacter baumannii.The DPPH and ABTS were significantly inhibited by methanolic extract of Bauhinia racemosa leaf with IC50 of 9 μg/ml and 550μg/ml respectively, whereas methanolic extract of leaves showed good antioxidant potential using ferric reducing power assay (1.896[s3]  and phosphomolybdate assay (108.12 mg AAE/g) methods.Conclusion: The results of present study showed that Bauhinia racemosa leaf possesses high potential antimicrobial and antioxidant activity and could be a potential source of natural antioxidant that could have great importance as therapeutic agents in preventing oxidative stress-related degenerative diseases.Keywords: Bauhinia racemosa, Antimicrobial, In vitro [s4] antioxidant, DPPH, ABTS, FRPA. [s1]italic [s2]italic [s3]IC50 or what? [s4]itali

Mechanistic Explorations of Antidiabetic Potentials of Sansevieria Trifasciata

ABSTRACT: There has been a great resurgence of interest in phyto-therapy in treating chronic diseases like Type 2 diabetes. The current research aims to explore the mechanistic anti-diabetic potentials of the leaves and rhizomes of Sansevieria trifasciata (ST). Chemo-profiling by phytochemical tests and GC-MS analysis have shown the presence of phenolics, alkaloids, terpenoids, flavonoids, saponins, steroids and glycosides. The median lethal dose was found to be 500 mg/kg on acute toxicity studies. The extract showed statistically significant (p<0.001 and p<0.05) hypoglycemia on fasting and oral glucose challenge; body weight (p<0.001) determination and quenching of TBARS (p<0.001); the facts being further supported by histopathological assessment. The flow cytometric data revealed the beneficial role of plant extract in preventing apoptotic cell death under hyperglycemic conditions and results of Western blot analysis showed reduced expressions of the vascular inflammation markers on administration of plant extract

PREPARATION, CHARACTERIZATION AND EVALUATION OF POLY (LACTIDE–CO–GLYCOLIDE) MICROSPHERES FOR THE CONTROLLED RELEASE OF ZIDOVUDINE

Objective: The purpose of this research work was to develop and evaluate microspheres appropriate for controlled release of zidovudine (AZT). Methods: The AZT loaded polylactide-co-glycolide (PLGA) microspheres were prepared by W/O/O double emulsion solvent diffusion method. Compatibility of drug and polymer was studied by Fourier-transform infrared spectroscopy (FTIR). The influence of formulation factors (drug: polymer ratio, stirring speed, the concentration of surfactant) on particle size encapsulation efficiency and in vitro release characteristics of the microspheres was investigated. Release kinetics was studied and stability study was performed as per ICH guidelines. Results: Scanning electron microscopy (SEM) images show good reproducibility of microspheres from different batches. The average particle size was in the range of 216-306 μm. The drug-loaded microspheres showed 74.42±5.08% entrapment efficiency. The cumulative percentage released in phosphate Buffer solution (PBS) buffer was found to be 55.32±5.89 to 74.42±5.08 %. The highest regressions (0.981) were obtained for zero order kinetics followed by Higuchi (0.968) and first order (0.803). Conclusion: Microsphere prepared by double emulsion solvent diffusion method was investigated and the results revealed that 216-306 μm microsphere was successfully encapsulated in a polymer. FT-IR analysis, entrapment efficiency and SEM Studies revealed the good reproducibility from batch to batch. The microspheres were of an appropriate size and suitable for oral administration. Thus the current investigation show promising results of PLGA microspheres as a matrix for drug delivery and merit for In vivo studies for scale up the technology

EVALUATION OF ANTIDEPRESSANT ACTIVITY OF ECLIPTA ALBA USING ANIMAL MODELS

Objective : Eclipta alba (Asteraceae) is a traditional medicinal plant known as Bhringaraj.This plant  has been used for the treatment of a variety of diseases. The leaves of Eclipta alba showed antihyperglycemic activity. The roots of Eclipta alba were found effective in wound healing . Methods : This study was undertaken to evaluate the possible antidepressant effect of  Eclipta alba leaf extract (EALE)  using Tail suspension test(TST) & Forced swim test (FST).  36 albino rats of either sex weighing between 20-25gm were randomly selected divided into 6 equal groups.  Group-I (control) received polyethyleneglycol (1ml/100gm),Group-II, III & IV received EALE in doses of 100,200,400 mg/kg orally (P.O.) respectively. Group V & VI (positive control) received Fluoxetine & Imipramine at doses of 20mg/kg & 15mg/kg p.o respectively.  Drug treatment was given for seven & fourteen successive days.  60 minutes after last dose of drug or standard the immobility period was recorded. Results : EALE produced significant antidepressant like effect at dose of 200 & 400 mg/kg administered for 7 & 14 consecutive days as indicated by reduction in immobility times of mice in TST & FST (P<0.05). The efficacy of EALE at 200mg/kg was found to be comparable to that of Fluoxetine & Imipramine at doses of 20mg/kg & 15mg/kg. Conclusion: The results of the present study indicate that EALE possesses significant antidepressant activity compared to that of both Fluoxetine & Imipramine. KEYWORDS: Eclipta alba , Forced swim test, Tail suspension test, Antidepressants, Immobolity tim