Multiparticulate Dosage Form Research Articles

Optimization and In Vitro Evaluation of Curcumin-loaded Calcium Alginate Microbeads using Box-Behnken Design for Colorectal Cancer

Background and Objective:: After lung cancer and breast cancer, colorectal cancer (CRC) is the third most common type of cancer and has the second-highest fatality rate. Curcumin is one such naturally occurring dietary compound that demonstrated promise to treat colon cancer. For that, the goal of the current study was to coat curcumin with Eudragit S100 to treat colorectal cancer in the distal intestine release. The multiparticulate dosage form can increase the solubility of curcumin in the colon environment, sustain the drug release, and protect the drug from abrupt degradation in the colon environment. All of these alterations can enhance the colon tissue levels, especially in the colon cancer cells in the patients, and thereby can enhance the utility of the therapy. Methods:: By using the ionotropic gelation technique, the formulations were made. Moreover, Design Expert 13 used a three-factor, three-level Box-Behnken design (BBD) in this work to optimize the formulation for colon-targeted drug delivery. The concentration of potassium alginate, the concentration of calcium chloride, and the curing duration were considered independent variables, and prepared microbeads were refined to study their impacts on entrapment effectiveness and particle size. Eudragit S100 was enteric coated on Calcium alginate beads with an improved core. Results:: Regarding particle size and entrapment effectiveness, respectively, the polymer concentration and curing duration had a substantial impact. The ideal concentrations of calcium chloride and potassium alginate were 15% w/v and 6% w/v, respectively, with a 20-minute curing time. With a drug entrapment efficiency of 88.4%, the improved formulation had particles with a size of 708 μm. After 12 hours, 79.23±0.32% of the drug was released following an enteric coating of Eudragit S100 of optimized calcium alginate microbeads (10% weight gain). Conclusion:: The present study conclusively demonstrates the usefulness of a Box-Behnken design in the optimization of colon-targeted formulations. To effectively treat colorectal cancer, enteric-coated calcium alginate microbeads can be administered orally to deliver curcumin precisely to the colon.

Preparation and Characterization of a Novel Multiparticulate Dosage Form Carrying Budesonide-Loaded Chitosan Nanoparticles to Enhance the Efficiency of Pellets in the Colon.

An attempt was made to conquer the limitation of orally administered nanoparticles for the delivery of budesonide to the colon. The ionic gelation technique was used to load budesonide on chitosan nanoparticles. The nanoparticles were investigated in terms of size, zeta potential, encapsulation efficiency, shape and drug release. Then, nanoparticles were pelletized using the extrusion-spheronization method and were investigated for their size, mechanical properties, and drug release. Pellets were subsequently coated with a polymeric solution composed of two enteric (eudragit L and S) and time-dependent polymers (eudragit RS) for colon-specific delivery. All formulations were examined for their anti-inflammatory effect in rats with induced colitis and the relapse of the colitis after discontinuation of treatment was also followed. The size of nanoparticles ranged between 288 ± 7.5 and 566 ± 7.7 nm and zeta potential verified their positive charged surface. The drug release from nanoparticles showed an initial burst release followed by a continuous release. Pelletized nanoparticles showed proper mechanical properties and faster drug release in acidic pH compared with alkaline pH. It was interesting to note that pelletized budesonide nanoparticles released the drug throughout the GIT in a sustained fashion, and had long-lasting anti-inflammatory effects while rapid relapse was observed for those treated with conventional budesonide pellets. It seems that there is a synergistic effect of nanoformulation of budesonide and the encapsulation of pelletized nanoparticles in a proper coating system for colon delivery that could result in a significant and long-lasting anti-inflammatory effect.

Ultra- sustained-release multi-particulate dosage form of Doxycycline as a platform of repurposing therapeutics in the fight against COVID 19: in-vitro and in-silico study

Ultra- sustained-release multi-particulate dosage form of Doxycycline as a platform of repurposing therapeutics in the fight against COVID 19: in-vitro and in-silico study

Viscosity of API/fatty acid suspensions: Pitfalls during analysis.

This article describes how to obtain reliable data during rheological analysis of active pharmaceutical ingredient/fatty acid suspensions. These materials are specifically used for prilling, an innovative pharmaceutical technique for the production of a multiparticulate dosage form. Nevertheless, presented guidelines are applicable for a wide range of pharmaceutical suspensions. Reliable rheological results can only be obtained when being aware of artefacts, such as a non-continuous medium, sedimentation, apparent wall slip and protrusion flow. To comply with the continuum hypothesis at high phase volumes (≥25% w/w), the required gap-to-particle-size ratio may be larger than the generally accepted 10:1 ratio. Reproducible flow curves that are not disturbed by sedimentation during sample analysis can be obtained faster by varying the shear rate stepwise from high to low values. While apparent wall slip (at low shear rates) can be prevented via serrated instead of smooth plates, protrusion flow (at high shear rates) during measurements with serrated plates results in non-reliable data. Therefore, in general, high viscous suspensions with yield stress can be analysed with serrated plates, while low viscous suspensions without yield stress should be analysed with geometries having smooth surfaces. By following these guidelines, accurate rheological properties of pharmaceutical suspensions can be obtained.

Development of bio-relevant dissolution method for prognosis of In-vivo performance of Dipyridamole from modified release capsules

In-vitro biorelevant dissolution test method was developed for Dipyridamole in modified release multi-particulate dosage form, to simulate the product drug release after oral administration to human. The Dipyridamole concentration in blood plasma achieved after oral administration under pre-prandial (fasting) condition were used for deriving the target dissolution profile deconvoluting the plasma concentration using numerical deconvolution technique. The fraction of drug absorbed was considered as the target dissolution profile. The drug product was tested by using the dissolution method recommended by office of generic drugs, and the dissolution results observed are not comparable with the target dissolution profile. Dissolution method was developed using reciprocating cylinder, Bio-Dis (apparatus -3 as per USP), by simulating the pre-prandial conditions. A full factorial design of experiment was carried out to achieve the target dissolution profile. Media volume and dips per minute (DPM) are considered as main factors, in design of experiment. The dissolution results achieved with media volume 250ml and 10DPM were found to be comparable with target dissolution profile and observed with the F2 value (similarity factor) of 92%. The developed dissolution method demonstrates a very good in-vitro/in-vivo correlation under pre-prandial condition, and shall be used as a predictive in-vitro tool for evaluation Dipyridamole extended release capsules.

Alginate Microspheres: The Innovative Approaches to Production of the Microbeads/Micro-Particles

Multiparticulate dosage form is pharmaceutical formulations where the active substance is in the form of a number of small independent subunit such as, granules, microparticle, beads, and microspheres. Multiparticulate drug delivery systems are specifically suitable for achieving delayed and sustained release oral formulations with a minimum risk of dose dumping, local irritation, systemic toxicity, and variation in rate of bioavailability as they are less dependent on gastrointestinal transit time and offers many advantages over unit particulate dosage forms. Microbeads are small, sphere shaped, systematically produced free-flowing properties, semi-spherical solid units. Microbeads are the agglomerates of about size ranging from 0.5 mm to 1.0 mm, obtained from various starting materials and utilizing different innovative techniques. A blend of multiparticulate can also be used to provide the desired drug release profile. These round shaped particles produced by mostly principle of atomization technique.Among various different innovative techniques Vibration technology, Electrostatic bead generator, Jetcutter technology, electrostatic forces, dropping method and a mechanical cutting device are few of many. In current article it describes about the total methods involved and their working principles with diagrams were clearly illustrated. Now a days sodium alginate beads were designed by these technologies mostly in relative to microencapsulation techniques.
 Keywords: Atomization, Vibrating technology, Jetcutter device, Electrostatic bead generator Dropping method and electro-spray technology

FORMULATION AND EVALUATION OF PECTIN-CALCIUM CHLORIDE BEADS OF AZATHIOPRINE FOR COLON TARGETED DRUG DELIVERY SYSTEM

Objective: Calcium pectinate is an insoluble hydrophilic material used for sustained release delivery. The objective of the study was formulation and evaluation pectin-calcium chloride beads of azathioprine.Methods: Calibration curves of azathioprine were prepared in 0.1N HCl solution (pH-1.2) and phosphate buffer (pH-6.8 and pH-7.4). Fourier transform infrared spectroscopy and differential scanning calorimetry was used to determine compatibility between azathioprine and excipients. Formulation and optimization of calcium-pectinate beads were performed. The coating of the optimized batch was performed with eudragit S100. Micrometric properties, scanning electron microscopy, in vitro azathioprine release, and stability study was performed. Dissolution kinetic study was assessed for various kinetics models of the optimized batch. The Wilcoxon test followed by the Dunnett’s multiple comparison tests were performed between uncoated and coated beads in vitro dissolution profile of optimized batch in 0.1N HCl after 2 h.Results: Fourier transform infrared spectroscopy and differential scanning calorimetry had identical peaks with that of pure azathioprine in compatibility study. Scanning electron microscopy of an uncoated optimized batch of beads indicated the smooth and uniform surface of prepared beads. Eudragit S100 coating was decreased release of azathioprine release in 0.1N HCl after 2 h (p = 0.049, q = 3.533). Korsmeyer/Peppa's model was applied with release exponent higher than 1. In vitro percentage cumulative azathioprine release was identical before and after stability study.Conclusion: Calcium pectinate beads of azathioprine, a multi-particulate dosage form using pH-dependent approaches were prepared.

Multi-Particulate Dosage Forms for Pediatric Use

In recent years, regulations on pediatric medicines have induced an increased need for research into novel childappropriate dosage forms. Indeed, children cannot be considered as « small adults » as they present different anatomical and physiological characteristics. Whatever the route of administration, the age-appropriateness of the formulation is of major importance and has to be taken into consideration. The development of new pediatric dosage forms encounters technical complexities such as dose modification, ease of administration/swallowing, tastemasking, chemical and physical stability, preservation, considerations of a multi-phase and/or multi-use product, packing, providing/designing the measuring device. Innovations are important and the research of new ways to deliver medicines tends to improve compliance, convenience and pharmacokinetic. Recently, the World Human Organization recommended that small sized solid forms or orally disintegrating solid forms should be favored. Solid multi-particulate systems such as pellets have the advantage to cover a broad range of doses for different patients. Dose adjustment can be accurately done by means of dosing device such as a multi-particulate counting device. Developing multi-particulate dosage form with fast disintegration can be useful for children as they present both advantages of solid and liquid formulations. This led to the concept of Orally Disintegrating Tablet which disintegrates rapidly in the mouth into small particles or pellets. Their small size enables them to be well distributed along the gastrointestinal tract improving the bioavailability while reducing local drug concentration, risk of toxicity and side effects. They offer easy swallowing and dose flexibility for pediatric patients and caregivers. The promising results of our fast disintegrating pellets used in multi-particulate dosage forms indicate that they might be the base of a solid platform technology for pediatric medicines.

Preparation and optimization of glyceryl behenate-based highly porous pellets containing cilostazol

The aim of this study was to prepare a highly porous multiparticulate dosage form containing cilostazol for gastroretentive drug delivery. The floating pellets were prepared with glyceryl behenate as a matrix former and camphor as a sublimating agent by extrusion/spheronization and sublimation under vacuum. Granules prepared with sublimation at 60 °C displayed a slower dissolution rate and smoother surface morphology than those prepared at lower temperatures. This was unexpected as the reported melting point of glyceryl behenate is higher than 69 °C. The DSC study revealed that melting began at a lower temperature owing to the multicomponent property of glyceryl behenate, which led to a sintering effect. The prepared pellets were spherical with unimodal size distribution. They also had porous structures with increased porosity, which led to immediate buoyancy. As cilostazol is a hydrophobic drug that has an erosion-based release mechanism, drug release profile was highly correlated with the percentage of disintegrated pellets. Various excipients were added to the glyceryl behenate-based formulation to increase the floating duration. When hydroxyethyl cellulose was added to the glyceryl behenate-based pellets, acceptable dissolution rate and buoyancy were acquired. This system could potentially be used for gastroretentive delivery of various hydrophobic drugs, which was generally considered difficult.

Assessment of distribution of pellets in tablets by non-destructive microfocus X-ray imaging and image analysis technique

In this study, potassium chloride (KCl) containing matrix pellets were compressed into tablets using powder or pellet form of partially spray dried lactose as filler-binder excipient. The spatial distribution of potassium chloride pellets within the tablets was examined by non-destructive microfocus X-ray imaging (MFX) and image analysis technique. The KCl content of the tablets was determined by conductivity measurement and these values were compared to the average gray values of the MFX images calculated by image analysis software. A linear relationship has been shown between the KCl content predicted from average gray values of the MFX images and the actual KCl content measured by conductometry. The non-destructive MFX method was capable to characterize the pellet distribution as well as the pellet content of the multiparticulate dosage form. Based on the observed spatial distribution of KCl pellets within the tablets made using lactose pellets or powder for direct compression as filler excipients the difference in homogeneity was not remarkable besides the applied blending method.

Development of pellets for oral lysozyme delivery by using a quality by design approach

The concept of Quality by design is of increasing importance in the pharmaceutical industry, especially in the development of biotechnologically produced active pharmaceutical ingredients (APIs). These proteins/peptide-like materials are usually more sensitive than small molecules to the environmental and process parameters.The objectives of the presented study were to identify how the critical process parameters influence the critical quality attributes (CQAs) of a lysozyme-containing multiparticulate dosage form, and to determine the critical points of API activity preservation. The experiments were performed according to a 26 factorial design. The process parameters were recorded with Process Analytical Technology tools, based on in-line mixing speed, mixer torque and temperature measurements and at-line moisture content analysis. The hardness and geometry of the pellets, and the activity of the API were studied as CQA. Complex relationships were identified between the CQAs and process parameters, and the thermomechanical effects and the liquid distribution inside the mass during the texture-forming steps of the process were found to exert considerable effects on the mechanical and geometrical properties and also basically to determine the API activity.

Feasability of a new process to produce fast disintegrating pellets as novel multiparticulate dosage form for pediatric use

Novel orally disintegrating system based on multiparticulate form was developed, offering an alternative to encounter major issues in the design of dosage form for pediatric patients, i.e., the difficulty in swallowing large solid dosage form (tablet or capsule), and the requirement to cover a broad range of doses for different age groups. Microcrystalline cellulose-based pellets containing acetaminophen were prepared via extrusion/spheronization followed by freeze-drying. The in vitro disintegration behavior of these pellets was quantitatively measured with a texture analyzer. Mercury intrusion and gas adsorption techniques, scanning electron microscopy of pellet surface and cross-section were performed in order to characterize their internal porous structure. Pellets characteristics such as size distribution, sphericity, friability and drug release were also determined. The developing process was able to produce pellets containing high drug loading (25, 50 and up to 75%, w/w) with good sphericity (aspect ratio ∼1) and low friability. The pellets exhibited an instantaneous disintegration upon contact with water, which was indicated by two parameters: the disintegration onset was approximating to 0, and the disintegration time less than 5s. The fast disintegration behavior is correlated with the pellet internal structure characterized by a capillary network with pore diameter varying from 0.1 to 10μm. Such a structure not only ensured a rapid disintegration but it also offers to freeze-dried pellets adequate mechanical properties in comparison with conventional freeze-dried forms. Due to pellet disintegration, fast dissolution of acetaminophen was achieved, i.e., more than 90% of drug released within 15min. This novel multiparticulate system offers novel age-appropriate dosage form for pediatric population owing to their facility of administration (fast disintegration) and dosing flexibility (divided and reduced-size solid form).

Interdiction of hypoglycemia in diabetic children by multiparticulate dosage form with controlled glucose release

Patients tend to evade the occurrence of hypoglycemic episodes by excessive carbohydrate intake. Glucose pellets with delayed release in the time of the maximum effect of insulin can not only prevent hypoglycemia but also eliminate the preventive carbohydrate intake. The pellets can be administered in a mixture with semisolid food.The cores containing glucose in combination with osmotically active agents (croscarmellose sodium, carmellose sodium, polyethylene glycol, or carboxymethyl starch) were prepared by extrusion–spheronization and coated with 15% water ethylcellulose dispersion (Surelease® B NF) in Wurster column (Medipo, Havlíčkův Brod, Czech Republic) into four coating levels (12.5, 25, 35, and 50%). Mean particle size is 0.63–0.73 for cores and 0.82–0.98 for coated pellets. Cores and coated pellets have excellent or good flow properties according to Hausner ratio and Carr index. Aspect ratio ranges from 1.78 to 2.17 for cores and from 1.73 to 2.31 for coated pellets. Dissolution was performed using pH-independent method and method with continual change of pH. The suitable pH-independent release was achieved in the samples containing carboxymethyl starch or polyethylene glycol. Glucose release is enabled by a membrane rupture caused by core swelling. It can be, therefore, assumed that the glucose release profile will not be affected by food or transit time.

Calendering as a direct shaping tool for the continuous production of fixed-dose combination products via co-extrusion

In this study calendering is used as a downstream technique to shape monolithic co-extruded fixed-dose combination products in a continuous way. Co-extrudates with a metoprolol tartrate-loaded sustained-release core and a hydrochlorothiazide-loaded immediate-release coat were produced and immediately shaped into a monolithic drug delivery system via calendering, using chilled rolls with tablet-shaped cavities. In vitro metoprolol tartrate release from the ethylcellulose core of the calendered tablets was prolonged in comparison with the sustained release of a multiparticulate dosage form, prepared manually by cutting co-extrudates into mini-matrices. Analysis of the dosage forms using X-ray micro-computed tomography only detected small differences between the pore structure of the core of the calendered tablet and the mini-matrices. Diffusion path length was shown to be the main mechanism behind the release kinetics. Terahertz pulsed imaging visualized that adhesion between the core and coat of the calendered tablet was not complete and a gradient in coat thickness (varying from 200 to 600μm) was observed. Modulated differential scanning calorimetry and X-ray diffraction indicated that the solid-state properties of both drugs were not affected by the calendering procedure.

Microencapsulation of a synbiotic into PLGA/alginate multiparticulate gels

Probiotic bacteria have gained popularity as a defence against disorders of the bowel. However, the acid sensitivity of these cells results in a loss of viability during gastric passage and, consequently, a loss of efficacy. Probiotic treatment can be supplemented using 'prebiotics', which are carbohydrates fermented specifically by probiotic cells in the body. This combination of probiotic and prebiotic is termed a 'synbiotic'. Within this article a multiparticulate dosage form has been developed, consisting of poly(d,l-lactic-co-glycolic acid) (PLGA) microcapsules containing prebiotic Bimuno™ incorporated into an alginate-chitosan matrix containing probiotic Bifidobacterium breve. The aim of this multiparticulate was that, in vivo, the probiotic would be protected against gastric acid and the release of the prebiotic would occur in the distal colon. After microscopic investigation, this synbiotic multiparticulate was shown to control the release of the prebiotic during in vitro gastrointestinal transit, with the release of galacto-oligosaccharides (GOS) initially occurred over 6h, but with a triphasic release pattern giving further release over 288 h. Encapsulation of B. breve in multiparticulates resulted in a survival of 8.0 ± 0.3 logCFU/mL cells in acid, an improvement over alginate-chitosan microencapsulation of 1.4 logCFU/mL. This was attributed to increased hydrophobicity by the incorporation of PLGA particles.

Application of active layering and coating techniques in the development of a multiparticulate, controlled release dosage form of a high-dose, highly soluble drug

Context: The success of the development of controlled release, multilayered, multiparticulate dosage form of a high-dose, highly-soluble drug is dependent upon proper material and processing choices.Objective: To develop a controlled release dosage form of diltiazem hydrochloride using active layering and coating.Methods: Active layering was achieved by spraying a drug solution onto sugar cores using polyvinyl alcohol – polyethylene glycol as a binder. Layered pellets with highest loading and lowest binder content were coated using aqueous dispersions of polyvinyl acetate (PVAc). The effects of the plasticizer and curing on drug release were evaluated.Results and discussion: The binder level had no effect on the process efficiency. Drug release from PVAc-coated pellets was slowed by increasing PVAc level. Plasticization slowed drug release in comparison to nonplasticized formulations. Curing affected drug release of nonplasticized formulations only. Protection against humidity was essential in stabilizing drug release under stability study conditions.Conclusion: Materials and process used were suitable to face the challenge posed by the high dose of the water-soluble drug on the success of the formulation. The effects of the plasticizer, curing and ability of packaging to protect against elevated humidity on the performance of the studied system should be considered in development.

Technological and biopharmaceutical optimization of nystatin release from a multiparticulate based bioadhesive drug delivery system

Formulation considerations of a new drug delivery system include controlling the site of release of the active ingredient, maintaining drug level for a suitable time and decreasing dosage frequency. In research and development practice, these therapeutic benefits can be attained by selecting suitable active ingredients and optimizing procedure parameters, determining the composition of the medicine, and dissolution properties.The aim of our study was to design a pharmaceutical preparation with increased local therapeutic effect in the therapy of gastrointestinal candidiasis. The polyene antibiotic nystatin may be an optimal choice for active agent, incorporated in a bioadhesive multiparticulate system. Choosing the proper excipients in the proper dosage form and ensuring prolonged residence time may further improve the optimal treatment. Using an experimental design, the micropellets were prepared with 5% nystatin content, taking the factors average pellet size (∼200 to ∼800μm) and the amount of applied carbomer and hydroxyethylcellulose (0–5%) into consideration. Dissolution of the active ingredient was detected by UV spectrophotometric and microbiological assay. The bioadhesive character of the multiparticulate dosage form was examined by ex vivo wash-off test. The only factor which significantly influenced the examined parameters was average pellet size. The proportion of applied bioadhesive excipients had significance mostly in interactions with average pellet size. Eventually, optimized drug release (5–10min mean dissolution time, 50–55% bioadhesion retention) could be achieved with 550μm pellet size, containing carbomer and hydroxyethylcellulose in 85:15 ratio.

Heuristic modeling of macromolecule release from PLGA microspheres

Dissolution of protein macromolecules from poly(lactic-co-glycolic acid) (PLGA) particles is a complex process and still not fully understood. As such, there are difficulties in obtaining a predictive model that could be of fundamental significance in design, development, and optimization for medical applications and toxicity evaluation of PLGA-based multiparticulate dosage form. In the present study, two models with comparable goodness of fit were proposed for the prediction of the macromolecule dissolution profile from PLGA micro- and nanoparticles. In both cases, heuristic techniques, such as artificial neural networks (ANNs), feature selection, and genetic programming were employed. Feature selection provided by fscaret package and sensitivity analysis performed by ANNs reduced the original input vector from a total of 300 input variables to 21, 17, 16, and eleven; to achieve a better insight into generalization error, two cut-off points for every method was proposed. The best ANNs model results were obtained by monotone multi-layer perceptron neural network (MON-MLP) networks with a root-mean-square error (RMSE) of 15.4, and the input vector consisted of eleven inputs. The complicated classical equation derived from a database consisting of 17 inputs was able to yield a better generalization error (RMSE) of 14.3. The equation was characterized by four parameters, thus feasible (applicable) to standard nonlinear regression techniques. Heuristic modeling led to the ANN model describing macromolecules release profiles from PLGA microspheres with good predictive efficiency. Moreover genetic programming technique resulted in classical equation with comparable predictability to the ANN model.

FORMULATION & DEVELOPMENT OF PELLETS OF TOLTERODINE TARTRATE: A QUALITATIVE STUDY ON WURSTER BASED FLUIDIZED BED COATING TECHNOLOGY

In recent pharmaceutical applications, multiparticulate dosage forms are gaining much importance over single-unit dosage forms. The purpose of designing multiparticulate dosage form is to develop a reliable formulation that has all the advantages of a single unit formulation and yet devoid of the danger of alteration in drug release profile and formulation behavior due to unit to unit variation. The aim of present work is qualitative study on formulation of multiparticulate modified release pellets of Tolterodine Tartrate, by “Wurster Based Fluidized Bed Coating Process”(layering technique).The main purpose of the present study was to investigate the feasibility of the wurster process for preparing extended release pellets and subsequently comparing the release profile of the pellets so prepared with a marketed reference product in various media. Additionally, the effects of some independent process variables were evaluated. The effect of the various process parameters i.e. inlet air temperature, product temperature, exhaust temperature, atomization speed, spray pump speed, atomization air volume and air flow on the wurster process was studied. The results suggested that the values of process parameters greatly vary with the physical properties of the drug, polymers and solvents used in process for layering of pellets. Key Words: non-pariel-seeds (N.P.S), E.R coating (extended release coating), Wurster technology, process parameters

A Comparative Study of Acyclovir icroencapsulation by Novel Solvent Evaporation-Matrix Erosion and Spray Drying Techniques

Designing and evaluating a multiparticulate controlled release dosage form, to increase the efficacy of acyclovir (a selective antiherpes agent). Spray drying technique for microsphere production is compared with novel solvent evaporation-matrix erosion technique for variable drug loading in different concentration of ethyl cellulose. The microspheres were characterized for physicochemical properties. The microspheres sizes were ranged from 7-25 μm. The spray dried microspheres had better encapsulation efficiency (up to 91%) compared to that of novel solvent evaporation-matrix erosion technique microspheres. Scanning electron microscopy confirmed spherical geometry due to high cross-linking density. Differential scanning calorimetry, Fourier-transform infrared spectroscopy and x-ray diffraction studies showed chemical stability and intactness of entrapped drug in the microspheres. In vitro release of acyclovir from spray dried microspheres continued for longer period compared to novel solvent evaporation-matrix erosion method. Overall, the release studies depended on the concentration of ethyl cellulose, extent of drug loading, and the technique used to prepare microspheres. Thus, marked retardation of drug release may provide a useful effective anti-retroviral drug therapy.