Abstract (original) (raw)
International Journal of Pharmacy and Pharmaceutical Sciences, 2017
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.
Comparitive Studies of Hydrophilic Polymers on Sustained Drug Delivery of Zidovudine
2015
The goal in designing sustained or controlled delivery is to reduce frequency of dosing or to increase the effectiveness of the drug by localization at the site of action, reducing the dose required, providing uniform drug delivery. The terms Sustained release, prolonged release, modified release, extended release or depot formulations are used to identify drug delivery systems that are designed to achieve or extend therapeutic effect by continuously releasing medication over an extended period of time after administration of a single dose. [6] Considering the scope and availability of the natural polymers the present research work was planned with karaya gum, kondagogu gum and synthetic polymer HPMC(K100) as matrixing agents for the sustaining the drug release.
Formulation and Release Characteristics of Zidovudine-Loaded Solidified Lipid Microparticles
Tropical Journal of Pharmaceutical Research, 2014
Purpose: To formulate and determine the release profile of zidovudine (AZT)-loaded solidified lipid microparticles (SLMs). Methods: Different concentrations (0, 1, 2, 3 and 5 %w/w) of zidovudine (AZT) were formulated into microparticles in melt dispersion of Phospholipon ® 90H and goat fat in the ratio 1:1, 2:1, 2:3 and 1:3 followed by lyophilization. They were characterized for particle size, yield, entrapment efficiency (EE) and loading capacity (LC). In vitro release kinetics and mechanism of release were assessed sequentially in simulated gastric fluid (SGF, pH 1.2)and simulated intestinal fluid (SIF, pH 7.2). Results: The ratio 1: 1 formulation was the most stable in terms of physical observation.. Particle size analysis indicated that the particles were irregular in shape with size ranging from 5.10 ± 0.10 to 13.40 ± 2.20 µm. Yield decreased with increase in drug concentrations in the SLMs formulations. EE data showed that the microparticles containing 1 % w/w of AZT had the highest entrapment efficiency of 74.0 ± 0.03 %. LC also decreased with increase in concentration of AZT. AZT tablet released most of its content within 5 min with a sharp decrease in the concentration but the SLMs maintained its release for 8 to 12 h in different batches Conclusion: The results show that drug content has influence on drug release from the SLMs, but not on the mechanism of release. Furthermore, dose dumping was avoided and drug release mechanism was mostly non-Fickian while for the reference (commercial) tablet, it was Fickian.
International Journal of Drug Delivery, 2013
The aim of the research was to study the stability, release profile, pharmacokinetic and biodistribution properties of zidovudine (AZT)-solidified reverse micellar microparticulate. Lipid matrices formulated with Phospholipon ® 90H and goat fat at ratios of 1:1, 2:1, 3:1 and 2:3 were used to prepare AZT-loaded SLM by melt dispersion followed by lyophilization. In vitro release studies of the drug were carried out using a sequential drug release method in both SGF (pH 1.2) and SIF (pH 7.2) while the in vivo drug release studies were carried out using Wistar albino rats. The result of our findings showed that the drug is compatibility with the lipid matrix with the 1:1 showing the most stable microparticle preparation which was then optimized. The formulations showed a concentration dependent increase in their concentration maximum (C max) with values of 116.05 µg/ml, 124.21 µg/ml, 128.95 µg/ml, 138.95 µg/ml and time to reach maximum concentration (T max) values of 5h, 8 h, 8 h, and 5...
Oral Sustained Release Tablets of Zidovudine Using Binary Blends of Natural and Synthetic Polymers
Biological & Pharmaceutical Bulletin, 2010
Oral sustained release matrix tablets of zidovudine (ZDV) were prepared using different types, proportions and blends of carbopol 71G (C71) and a plant gum obtained from Abelmoschus esculentus (AEG). The effect of various formulation factors like polymer proportion, polymer type and pH of the dissolution medium on the in vitro release of the drug was studied, using the half change technique, in 900 ml of dissolution medium, at 100 rpm. Release kinetics were analyzed using Zero-order, Higuchi's square-root and Ritger-Peppas' empirical equations. In vitro release performance as revealed by the time taken for 70% of the drug to be released (t 70%), showed that the release rate decreased with increase in polymer proportion. Matrix tablets containing 10 and 20% AEG were found to exhibit immediate-release characteristics. Matrix tablets containing 30% AEG showed t 70% value of 204 min and extended the release up to 5 h, while matrix tablets containing 30% carbopol showed t 70% value of 234 min and extended the release up to 6 h. Three blends of AEG and C71 at the ratio of 1 : 2, 2 : 1 and 1 : 3 showed t 70% values of 132, 312 and 102 min respectively and extended the release up to 8 h. Mathematical analysis of the release kinetics indicated that the nature of drug release from the matrix tablets followed Fickian and anomalous release. Drug release from matrix tablets of zidovudine containing blends of AEG and C71 demonstrates the advantage of blending a natural and synthetic polymer over single polymer use.
The Influence of the Compression Force on Zidovudine Release from Matrix Tablets
AAPS PharmSciTech, 2010
The aim of the present work is the study of different zidovudine (AZT) formulations containing polymers (both cellulosic and acrylic), in order to evaluate the influence of the compression force on the antiviral release from the matrix tablets. The results evidenced that the formulations compressed at 500 and 1,000 MPa exhibit a higher hardness than those prepared at 100 MPa. The effect of the compression force on the drug release was analyzed and a statistically significant difference was observed (P<0.05). Using lower compression forces leads to slightly better release profiles, i.e., profiles close to an ideal Higuchi kinetics for a total release of drug in a 12-h period, allowing to conclude that a compression force higher than 100 MPa is unnecessary.
International Journal of Pharmaceutics, 1996
The objective of the present investigation was to improve the efficiency of encapsulation of zidovudine (AZT) in poly(lactide/gycolide) (PLGA 50:50) by modifying the secondary aqueous phase. Surface morphology of the microcapsules was unchanged during the partial saturation of the aqueous phase with calcium chloride. However, partial saturation of the aqueous phase with AZT and a change in the pH of the aqueous phase showed significant effect on the surface morphology. The surface appeared to be wrinkled when the pH of the aqueous phase was adjusted to 10. The particle size was between 8 and 18/tm. The particle size was increased significantly (78 140/~m) when the aqueous phase was partially saturated with AZT (0.25-0.75"/,,). The efficiency of encapsulation did not change when the aqueous phase was partially saturated with calcium chloride (5-30%). The efficiency of encapsulation was pH dependent. The encapsulation increased up to 17% when the aqueous phase was partially saturated with 0.75% AZT. The cumulative drug release from the microcapsules was between 15 and 34% within the first 24 h. A sustained drug release continued up to 60 days.
Glutaraldehyde cross-linked chitosan microspheres for controlled delivery of Zidovudine
Journal of Microencapsulation, 2009
Zidovudine-Chitosan microspheres were prepared by a suspension cross-linking method. The chitosan was dissolved in 2% acetic acid solution and this solution was dispersed in the light liquid paraffin. Span-80 was used as an emulsifier and glutaraldehyde as cross-linking agent. The prepared microspheres were slight yellow, free flowing and characterized by drug loading, infrared spectroscopy (IR), differential scanning colorimetry (DSC) and scanning electron microscopy (SEM). The in-vitro release studies are performed in pH 7.4 buffer solution. Microspheres produced are spherical and have smooth surfaces, with sizes ranging between 60-210 mm, as evidenced by SEM and particle size analysis. The drug loaded microspheres showed up to 60% of entrapment and release was extended up to 18-24 h. Among all the systems studied, the 35% Glutaraldehyde crosslinked, microspheres with 1 : 6 drug/chitosan ratio showed 75% release at 12 h. The infrared spectra and DSC thermograms showed stable character of zidovudine in the drug loaded microspheres and revealed the absence of drug-polymer interactions. Data obtained from in vitro release were fitted to various kinetic models and high correlation was obtained in the Higuchi model. The drug release was found to be diffusion controlled.
Asian Journal of Pharmaceutical and Clinical Research, 2013
The aim of the present study is to develop and evaluate natural biodegradable microcapsules of zidovudine (AZT) by using olibanum resin as microencapsulating agent, which after oral administration could improve the bioavailability of the drug, in order to provide the sustained release to minimize the dose dependent side effects as well as to improve patient compliance. The proposed system was evaluated in vitro for particle morphology, microencapsulation efficiency, production yield, micromeritic properties, release profile and release kinetics etc. Physico-chemical characteristics of AZT and AZT loaded microcapsules were evaluated by differential scanning calorimetry (DSC), X-ray diffraction (XRD), and infrared spectroscopy (FTIR). The resin coated microcapsules were found to be spherical, discrete and free flowing. Microencapsulation efficiency was in a narrow range (81-88%) suggesting an identical distribution of drug in different batches. DSC and XRD results showed a partial modification in AZT's solid state. Zidovudine release from optimized batches of resin coated microcapsules was slow and over 24 hours depending on the core: coat ratio. Drug release was found to be following Fickian diffusion mechanism. The resin coated microcapsules exhibited good controlled release characteristics and were found to be suitable for once a day oral controlled release product.
Goodness of fit Model Dependent Approaches of Controlled Release Matrix Tablets of Zidovudine
Indian Journal of Pharmaceutical Education and Research, 2016
Objectives: The objective of the study was to develop controlled release matrix tablet of zidovudine and to understand the release kinetics of drug by applying several mathematical model dependant and independent approaches. Various equations and models are developed for evaluating the drug release. Comparison of original and predicted release profile was most common way for selection of optimum formulation. Methods: In this study drug release profiles are characterized by using several parameters like percentage of drug released at 1 h and 12 h (R 1h , R 12h), dissolution efficiency at 2 h and 12 h (DE 2h , DE 12h) and pair wise procedures such as similarity factor (f 1), difference factor (f 2) and rescigno indices (ξ 1 , ξ 2) for getting the optimum formulation. Six batches (C1 to C6) of different concentration of carbopol embedded controlled release matrix tablets of Zidovudine were evaluated. Further the criteria for selection of appropriate model was based on goodness of fit (R 2 , adj-R 2), sum square residual (SSR), F value and Akaike Information Criterion (AIC). Results & Conclusion: Formulation C5 showed highest values of DE 2h , DE 12h (19.45%, 57.63%) with acceptance criteria of f 2 (51.63), f 1 (9.91), ξ 1 (0.063) and ξ 2 (0.066). Further, drug release from optimum batch C5 was explained by the Higuchi model, due to highest value of R 2 (0.992), adj-R 2 (0.991) with lowest value of SSR (62.22), F (5.65) and AIC (53.56) data. Moreover a simple mathematical equation was applied to determine the deviation of area under curve (AUC) between predicted and observed dissolution data. On an average of 13.4% percent deviation of AUC was observed in optimum batch.