RELATIVE COMPARISON OF STABILITY AND DEGRADATION OF METHYLCOBALAMIN TABLETS OF DIFFERENT BRANDS AT DIFFERENT STORAGE SETTINGS

Objective: To assess relative comparison of stability and degradation of Methylcobalamin tablets of different brands at various storage circumstances. Methods: The comparative in vitro study of Methycobal (innovator brand) with its other 5 different brands Cobalamin, Neuromet, Incobal, Qbal and Mecobal was organized for evaluation of physicochemical features of hardness, thickness, friability, weight variation, disintegration time and accelerated stability at 3 temperatures, 25 °C, 30 °C±65 % and 40 °C±75 % respectively for 3 mo. Later all brands were passed through HPLC for checking the extent of degradation of drug products. Results: All tablet brands were within the weight variation specified limits except Mecobal with a relative standard deviation of 6.83%. The weight variation values of Methycobal, Cobalamin, Neuromet, Incobal, Qbal and Mecobal were 0.29%, 0.11%, 0.09%, 0.13%, 0.09% and 0.14% after friability test respectively as per standard limits. The average thickness of Cobalamin, Incobal and Mecobal were not within specified limits. The average hardness of all trades was within limits except Cobalamin and Mecobal exceeding 6kp. The disintegration time of all companies was as per specifications. Conclusion: Qbal was found economical and cost-effective. However, study facts unveiled no noteworthy variety in the Q. C assessments of Methylcobalamin brands

Nanosponge-based hydrogel preparation of fluconazole for improved topical delivery

Purpose: To develop polymeric nanosponge based hydrogel system of fluconazole (FZ) for improved delivery for topical application.Method: Six different nanosponge preparations of fluconazole were formulated by oil-in-water (o/w) emulsion solvent diffusion method using various drug to polymer (ethylcellulose, EC) ratios. Polyvinyl alcohol (PVA) and dichloromethane were used to prepare the aqueous and dispersed phases, respectively. The nanosponges (NS) were studied for entrapment efficiency, particle size, structural properties, size and appearance, and in vitro drug release. Furthermore, the hydrogel formulation was evaluated for ex vivo permeation characteristics.Results: Morphological studies revealed porous nanosized particles with the outer surface resembling orange peel. The nanosponges had particle size in the range of 220.2 ± 4.5 to 624.1 ± 10.4 nm. Release studies showed 43.9 ± 3.2 % drug release at 6 h, confirming the sustained release pattern of the drug-loaded nanosponges. Powder x-ray diffraction (PXRD) and Fourier transform infra-red (FTIR) analyses indicate complex formation in the nanosponge structure. Out of six nanosponge formulations prepared, F3 containing FZ and EC in the ratio of 1:0.7 showed optimum physicochemical and release characteristics and, therefore, was selected for hydrogel formulation. Kinetic analysis of the permeation data revealed a Higuchi diffusion pattern. Ex vivo permeation studies indicate that the hydrogel preparation displayed adequate drug permeation through rat abdominal skin.Conclusion: A nanosponge-loaded hydrogel of fluconazole for improved permeation of the drug through skin has been successfully developed. Safety and toxicity tests are required to ascertain its potential suitability for use in humans.Keywords: Fluconazole, Nanosponges, Ethylcellulose, Drug release, Franz diffusion cell, Higuchi diffusio

Bioequivalence evaluation of new microparticulate capsule and marketed tablet dosage forms of lornoxicam in healthy volunteers

Purpose: To compare oral bioavailability and pharmacokinetic parameters of different lornoxicam formulations and to assess similarity in plasma level profiles by statistical techniques.Methods: An open-label, two-period crossover trial was followed in 24 healthy Pakistani volunteers (22 males, 2 females). Each participant received a single dose of lornoxicam controlled release (CR) microparticles and two doses (morning and evening) of conventional lornoxicam immediate release (IR) tablet formulation. The microparticles were prepared by spray drying method. The formulations were administered again in an alternate manner after a washout period of one week. Pharmacokinetic parameters were determined by Kinetica 4.0 software using plasma concentration-time data. Moreover, data were statistically analyzed at 90 % confidence interval (CI) and Schuirmann’s two one-sided t-test procedure.Results: Peak plasma concentration (Cmax) was 20.2 % lower for CR formulation compared to IR formulation (270.90 ng/ml vs 339.44 ng/ml, respectively) while time taken to attain Cmax (tmax) was 5.25 and 2.08 h, respectively. Area under the plasma drug level versus time (AUC) curve was comparable for both CR and IR formulations. The 90 % confidence interval (CI) values computed for Cmax, AUC0-24, and AUC0- , after log transformation, were 87.21, 108.51 and 102.74 %, respectively, and were within predefined bioequivalence range (80 - 125 %).Conclusion: The findings suggest that CR formulation of lornoxicam did not change the overall pharmacokinetic properties of lornoxicam in terms of extent and rate of lornoxicam absorption.Keywords: Analgesic, Microparticles, Controlled release, Lornoxicam, NSAIDs, Pharmacokinetic

Formulation Optimization and In-vitro Evaluation of Oral Floating Captopril Matrix Tablets using Factorial Design

Purpose: To develop a zero-order sustained release floating formulation of captopril, and optimize its drug release for enhanced oral bioavailability.Methods: A relatively new approach, 32 full factorial design, was used to formulate floating captopril matrix tablets and to systematically optimize its drug release using varying levels of xanthan gum and hydroxypropyl methylcellulose (HPMC) K100M polymers. Calcium carbonate was used as gasgenerating agent. After setting the levels by preliminary trials, nine tablet formulations (F1 - F9) were prepared by wet granulation method using Design Expert Software® - suggested combinations of polymers. The concentrations of HPMC K100M (X1) and xanthan gum (X2) were chosen as control variables. Conversely, the response variables selected were timed to release 50 % of the drug (t50%) at 6 h (Q6) and 12 h (Q12). Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) were used to assess compatibility between the drug and the excipients. The validity of the developed mathematical equations was assessed by designing three extra check-points.Results: The response surface plots drawn demonstrated the suitability of the hydrophilic matrixforming agents for formulating controlled release floating tablets of captopril. FTIR and DSC spectra showed no noticeable incompatibility between drug and polymers in both physical mixtures and in formulations. Floating time lag remained < 5.5 min with floating duration > 12 h. Considerable agreement was observed between predicted and actual release parameters. Fitting the data into different kinetic models showed that non-Fickian behavior for diffusion exponent (n) differed from 0.588 and 0.811.Conclusion: Optimum formulation (F4) showed satisfactory release profile. Moreover, the study successfully demonstrated influence of polymer blends in controlling release variables.Keywords: Captopril, Xanthan gum, Hydroxy propyl methyl cellulose , Factorial design, Bioavailabilit

Comparison of solvent evaporation and ultrasonicassisted production methods in the development of nimesulide nanosponges and their characterization

Purpose: To compare solvent evaporation and ultrasonic assisted synthesis in preparation of nimesulide nanosponges using polyvinyl-alcohol and Eudragit L100 as a polymer/copolymer and dichloromethane as a cross linker.Methods: Twelve formulations of nimesulide were prepared, six with each method by varying the ratios of both polymer and co-polymer. The resulting nanosponges were evaluated characterized by preformulation studies, production yield (%), differential scanning calorimeter, x-ray diffraction, Fourier transformation infrared spectroscopy, scanning electron microscopy, entrapment efficiency (%), actual drug content (%) and in-vitro dissolution studies.Results: The results revealed that the formulation with high amounts of co-polymer in both methods showed crystalline structures with enhanced dissolution rates in basic media. Drug entrapment was higher for products prepared by solvent evaporation method (74 %) than that prepared by ultrasonic assisted method (61 %). This correlates with the enhanced dissolution rates for products by solvent evaporation method and increased solubility due to drug-polymer complex formation.Conclusion: Formulations made by solvent evaporation method demonstrate higher production yield and drug entrapment. However, both methods exhibit enhanced dissolution rates in basic medium generally as well as other characteristics that are comparable to nanosponges reported in the literature with regard to their comb like structure

SCREENING OF VARIOUS BOTANICAL EXTRACTS FOR ANTIOXIDANT ACTIVITY USING DPPH FREE RADICAL METHOD

Aiming at the exploration of herbal use by society, crude extracts of the seeds of some commonly used medicinal plants (Vitis vinifera, Tamarindus indica and Glycin max) were screened for their free radical scavenging properties using ascorbic acid as standard antioxidant. Free radical scavenging activity was evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) free radical. The overall antioxidant activity of grape seeds (Vitis vinifera) was the strongest, followed in descending order by soybean (Glycin max) and tamarind (Tamarindus indica). The seeds extract of Vitis vinifera, Glycin max and Tamarindus indica showed 85.61%, 83.45% and 79.26%, DPPH scavenging activity respectively

Sustainable supply chain management: Confirmation of a higher-order model

Drawing from the research of green supply chain management and corporate social responsibility, this research proposes a hierarchical structure of sustainable supply chain management and develops a multi-item measurement scale to reflect the specific management practices of sustainable supply chain management. In this research, sustainable supply chain management is operationalised as a third-order factor reflected by three second-order factors, namely external green supply chain management, internal green supply chain management and corporate social responsibility. Utilising a rigorous, multi-step scale development method and data from 293 Chinese manufacturers, this research validates a 31-item measurement scale and approves the proposed third-order structure. The results confirm the multidimensionality of sustainable supply chain management, which suggests that it is necessary for the future researches to consider both environmental and social aspects. The valid measurement scales provide managers with a “to do list” to make the specific business decisions to achieve sustainable development in the supply chain

Relevant influence of promotional tools by pharmaceutical industry on prescribing behaviors of doctors: A cross-sectional survey in Pakistan

Worldwide drug expenditures have been one of the main concerns of health care managers, and its containment is one of the primary goals of health care authorities. The present study was conducted through a cross sectional survey in Pakistan during January to June, 2010 not only to find out the importance and influence of promotional tools used by pharmaceutical industry on prescribing behaviors of doctors/consultants, but to also establish comparison between doctors/consultants versus medical representatives and consultant versus doctors with an auxiliary of difference between local and multinational company's representative. The study revealed that promotional tools are considered vital from doctors and medical representatives' point of view. There exists significant difference in doctors and consultant's perception for sponsorships and low value gifts, but no difference in scientific promotional tools. No significant difference exits in perception of medical representatives of multinational and local company representatives. The companies tried to come up as per expectations of doctors to build its reputation and good image by employing different promotional tools. The study also revealed that marketing managers, product managers, chief executive officers or any decision makers involved in budget allocations and making promotional strategy should not rely heavily on medical representative's feedback as their perception is different from doctors/consultants about relevant importance of each promotional tool. The study will also help product managers and CEOs while allocating promotional budgets and developing promotional mix strategy, to gain maximum return out of investment. Detailed doctors' demographics can further be researched as predictor for preferring any promotional tools

Development and Pharmacokinetic Evaluation of Novasomes for the Trans-nasal Delivery of Fluvoxamine Using Arachidonic Acid-Carboxymethyl Chitosan Conjugate

Depression is the major mental illness which causes along with loss of interest in daily life, a feeling of hopelessness, appetite or weight changes, anger and irritability. Due to the hepatic first-pass metabolism, the absolute bioavailability of fluvoxamine (FVM) after oral administration is about 50%. By avoiding the pre-systemic metabolism, nasal delivery would boost bioavailability of FVM. Additionally, the absorption is anticipated to occur more quickly than it would via the oral route because of the existence of microvilli and high vasculature. A nonionic surfactant, cholesterol and an arachidonic acid-carboxymethyl chitosan (AA-CMCS) conjugate were used to develop FVM-loaded novasomes. To investigate the effects of surfactant concentration, AA-CMCS conjugate concentration and stirring speed on the novasomes’ characteristics, a Box–Behnken design was used. The dependent variables chosen were zeta potential, polydispersity index and particle size. The AA-CMCS conjugate was confirmed by 1H-NMR and FTIR. Using Design Expert software (version 7; Stat-Ease Inc., Minneapolis, MN, USA), novasomes were further optimized. The chosen optimal formulation (NAC8) was made up of AA-CMCS conjugate, Span 60 and cholesterol. Particle size, zeta potential and PDI values for NAC8 formulation were 101 nm, −35 mV and 0.263, respectively. The NAC8 formulation’s DSC and TGA analysis demonstrated that the medication had been uniformly and amorphously distributed throughout the novasomes. The NAC8 formulation showed 99% and 90% FVM release and permeation, respectively, and the novasome adherence time was 24 h. An improved antidepressant effect along with five-fold increase in bioavailability of FVM was observed after trans-nasal administration of NAC8 formulation compared to the reference commercially available Flumin® tablets. FVM-loaded novasomes administered via the nasal route may therefore constitute an advancement in the management of depression