Multiparticulate Dosage Forms Research Articles

Taste-masking methods in multiparticulate dosage forms with a focus on poorly soluble drugs.

In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Real-Time Cone-Growth Model for Determination of Pharmaceutical Powder Flow Properties.

The flow properties of pellets or granules are crucial for further processing drug dosage forms. Optimal compression or filling of multiparticulate dosage forms into capsules is influenced by forces between discrete particles, which could be partially characterized by flow properties. Several techniques have been developed to examine flowability, including static and dynamic methods applying empirical studies and up-to-date chaos theory; however, the newest methods seem only to be powerful with the supplementation of empirical principles. Our experiments try to refine both the technique of analysis and the methods, by finding new, alternative ways. Our approach to the flowability measurements was to set up a dynamic time-dependent model that combined empirical observations and chaos theory on a geometrical basis, thus finding new characteristics regarding the flow properties of pellets and granules that could be relevant for drug developers. Our findings indicate that sphericity and particle size are the most significant factors influencing the flowability of pharmaceutical multiparticular preparations. Furthermore, this study confirms that integrating chaos theory and empirical observations in a time-dependent dynamic model provides a comprehensive understanding of particle flow behavior, pivotal for optimizing manufacturing processes.

Binary isobaric phase diagrams of stearyl alcohol-poloxamer 407 formulations in the molten and solid state

Multiparticulate formulations allow for the design of specialized pharmaceutical dosage forms that cater to the needs of a wide range of patient demographics, such as pediatric and geriatric populations, by affording control over the release rate and facilitating the formulation of fixed-dose combination drugs. Melt spray-congealing (MSC) is a method for preparing multiparticulate dosage forms from a suspension or solid solution of active pharamaceutical ingredients (API) and a molten carrier matrix. Stearyl alcohol and poloxamer 407 mixtures are widely used as carrier matrices in MSC microsphere formulations. In this report, the phase equilibria of stearyl alcohol-poloxamer 407 mixtures were investigated by generating binary phase diagrams of composition, i.e. weight/weight percent of poloxamer 407 in stearyl alcohol, and temperature in the molten form and the solid state. The phase equilibria of the molten state were characterized by 1H NMR measurements. The miscibility curves of stearyl alcohol-poloxamer 407 molten mixtures revealed that stearyl alcohol and poloxamer 407 are not miscible in all proportions and that miscibility substantially increases with temperature. The phase equilibria of the solid state were characterized by DSC and PXRD experiments. The phase diagrams of the solid state indicate that stearyl alcohol and poloxamer 407 crystallize and melt separately and, thus, do not form a eutectic or a single phase. The phases equilibria of the bulk mixtures were compared to the phases observed in placebo MSC microspheres and it was determined that the microspheres consist of a mixture of thermodynamically stable and metastable stearyl alcohol crystals immediately after manufacture.

A systematic approach for assessing the suitability of enteral feeding tubes for the administration of controlled-release pellet formulations

Enteral nutrition plays an important role for patients who are unable to properly swallow food. In such patients, enteral feeding tubes are often used, through which food, but often also oral medications, are administered. However, this can pose the risk of tube clogging. Compared to the administration of crushed tablets, multiparticulate dosage forms are often considered easier to administer and furthermore have the advantage of enabling the administration of even controlled-release preparations. The objective of this systematic study was to identify tube- and formulation-related factors that contribute to successful administration of coated pellet formulations via a variety of commercially available feeding tube devices. The suitability of enteral feeding tubes for the administration of controlled-release pellet formulations that differed in size and type of starter core and functional coating was investigated in a stepwise approach using a novel in vitro setup. Results of the study indicate that pellet diameter and inner diameter of the feeding tube are by no means reliable parameters for estimating the tube’s suitability for pellet administration, but that many other tube and formulation-related factors and combinations thereof must be considered to ensure safe and effective drug administration via enteral feeding tubes.

STUDY OF INFLUENCE OF FORMULATION AND PROCESS VARIABLES ON ENTRAPMENT EFFICIENCY AND PARTICLE SIZE OF FLOATING MICRO BALLOONS OF DIPYRIDAMOLE BY DOE

Objective: In the current research work, dipyridamole, a BCS class–II drug, was aimed to be formulated as floating controlled release microballoons using ethyl cellulose as polymer and span 80 as surfactant to improve the gastric retention of drug as the multi-particulate dosage forms have tremendous advantages over single unit dosage forms.
 Methods: Microballoons were prepared by the emulsion solvent evaporation method. Prepared microballoons were characterized for entrapment efficiency, particle size, floating behavior and drug release studies. The study of effect of various formulation and process parameters like surfactant concentration, solvent volume, the volume of internal phase, polymer concentration, rotation speed on the drug entrapment efficiency and particle size of the microballoons were carried by using Box–Benhken to optimize the formulated microballoons.
 Results: The smallest particle size of the microballoons was found to be 205.9 µm in the F32 formulation. The highest drug entrapment efficiency was found to be 93.4% in the F34 formulation. Buoyancy studies showed all the formulations have good floating characteristics that lasted for a minimum of 24 h. The maximum yield of microballoons was found in the F7 formulation with 91.8% yield. The final results were statistically treated using ANOVA and were found to be significant (p value<0.05).
 Conclusion: Thus, the obtained results and their statistical interpretations indicated floating microballoons of dipyridamole were formulated effectively.

PULSATILE DRUG DELIVERY SYSTEM: A FORMULATION APPROACH FOR TREATMENT OF DISEASES

location at a particular time. Some of the conditions under which pulsatile drug delivery system is positive include duodenal ulcer, cardiovascular disease, arthritis, asthma, diabetes, neurological disorder, cancer, hypertension, and hypercholesterolemia. Pulsatile drug delivery systems are essentially time-controlled drug delivery systems in which the lag time is regulated independently of environmental factors such as pH, enzymes, gastrointestinal motility, etc. The theory justification for the use of pulsatile release is for drugs where a continuous release of drugs is not needed, i.e. a zero-order release. Drug administration in chronopharmacotherapy is coordinated with biological rhythms to achieve full therapeutic effect and minimize harm to the patient. This drug delivery system is designed to distribute drugs in accordance with body clock. The pulse must be designed in such a way as to achieve a total and rapid release after the lag time.
 Pulsatile drug delivery is therefore one device that provides strong promises of benefit to patients suffering from chronic conditions such as arthritis, asthma, hypertension by delivering medication at the right time, right place and in appropriate quantities. In recent pharmaceutical applications involving pulsatile delivery; multi-particulate dosage forms (e. g. pellets) over single-unit dosage forms are gaining more popularity. On the basis of methodologies, various pulsatile technologies have been developed, including ACCU-BREAKTM, AQUALON, CODAS ®, PRODAS ®, SODAS ®, MINITABS ®, DIFFUCAPS ®, OROS ® etc.

Oral Modified Release Multiple-Unit Particulate Systems: Compressed Pellets, Microparticles and Nanoparticles.

Oral modified-release multiparticulate dosage forms, which are also referred to as oral multiple-unit particulate systems, are becoming increasingly popular for oral drug delivery applications. The compaction of polymer-coated multiparticulates into tablets to produce a sustained-release dosage form is preferred over hard gelatin capsules. Moreover, multiparticulate tablets are a promising solution to chronic conditions, patients’ adherence, and swallowing difficulties if incorporated into orodispersible matrices. Nonetheless, the compaction of multiparticulates often damages the functional polymer coat, which results in a rapid release of the drug substance and the subsequent loss of sustained-release properties. This review brings to the forefront key formulation variables that are likely to influence the compaction of coated multiparticulates into sustained-release tablets. It focusses on the tabletting of coated drug-loaded pellets, microparticles, and nanoparticles with a designated section on each. Furthermore, it explores the various approaches that are used to evaluate the compaction behaviour of particulate systems.

A brief review on recent advances of extended release technology employed to design the oral dosage forms

The benefits offered by modified release systems include reduced dosing frequency with improved patient compliance, better and more uniform clinical effects with lower incidence of side effects and possible enhanced bioavailability. Characteristics of a modified release system as stated by USP is “The drug release characteristics of time, course and / or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional dosage forms” [1]. This includes technologies that modify the site of drug delivery. Extended release dosage forms extend the life of a drug so that dosage regiment shifts from 3 times a day dosing just once or twice a day. The successful formulation of a modified release device requires a comprehensive understanding of the mechanism of drug release from the macroscopic effects of size, shape and structure through to chemistry and molecular interaction. Multiparticulate dosage forms shown to be less prone to food effects than monolithic and is often the preferred formulation for extended and / or delayed release. Extended release drug formulation is conventionally produced as compressed tablets by hydrogel tablet technology. To produce these extended release tablet dosage forms, active ingredient is conventionally compounded with cellulose ethers like methylcellulose, ethyl cellulose or hydroxyl propyl methylcellulose with or without excipients and the resulting mixture is pressed into tablets. When the tablets are orally administered, cellulose ethers in the tablet swell upon hydration from moisture in the digestive system, thereby limiting exposure of active ingredient to moisture. As the cellulose ethers are gradually leached away by moisture, water more deeply penetrates the gel matrix and the active ingredient slowly dissolves and diffuses through the gel, making it available for absorption by the body. An appropriately designed controlled release drug delivery system can be a major advance towards solving problems concerning the targeting of a drug to specific organ or tissue and controlling the rate of drug delivery to the target sites. The development of the oral controlled release system has been a challenge to formulation scientists due to their inability to restrain and localize the system at targeted areas of the gastro intestinal tract. Matrix type drug delivery systems as carriers for the active ingredients are interesting and promising option in developing an oral controlled release system. Tablets are the preferred dosage form for many drugs and are still the most widely used formulations for both new and existing modified released products.

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.

Multi-particulate Systems: Cutting-edge Technology for Controlled Drug Delivery.

In the last two decades, multi-particulate dosage forms have caught the attention of formulation scientists due to their tremendous potential as a drug delivery system with a broad range of applications. Recent patented technologies are focused on designing multi-particulate systems that can enhance therapeutic efficacy and oral bioavailability with minimum systemic toxicity. The technologies offer opportunities to the manufacturers for increasing their market share, especially for competitive generics, and also establishing intellectual property positions. The present paper provides an overview of advanced technologies and patents, based on different principles, for designing multi-particulate dosage forms. The review covers basic characteristics of the current technologies, the mechanisms by which they overcome the limitations of conventional oral dosage forms, and their applications. Comprehensive knowledge of these technologies will expedite further development and platform technologies for multi-particulate controlled drug delivery systems.

Empirical search for factors affecting mean particle size of PLGA microspheres containing macromolecular drugs

Background and objectivesPoly(lactic-co-glycolic acid) (PLGA) has become one of the most promising in design, development, and optimization for medical applications polymers. PLGA-based multiparticulate dosage forms are usually prepared as microspheres where the size is from 5 to 100 µm, depending on the route of administration. The main objectives of the study were to develop a predictive model of mean volumetric particle size and on its basis extract knowledge of PLGA containing proteins forming behaviour. MethodsIn the present study, a model for the prediction of mean volumetric particle size developed by an rgp package of R environment is presented. Other tools like fscaret, monmlp, fugeR, MARS, SVM, kNNreg, Cubist, randomForest and piecewise linear regression are also applied during the data mining procedure. ResultsThe feature selection provided by the fscaret package reduced the original input vector from a total of 295 input variables to 10, 16 and 19. The developed models had good predictive ability, which was confirmed by a normalized root-mean-square error (NRMSE) of 6.8 to 11.1% in 10-fold cross validation training procedure. Moreover, the best models were validated using external experimental data. The superior predictiveness had a model obtained by rgp in the form of a classical equation with a normalized root-mean-squared error (NRMSE) of 6.1%. ConclusionsA new approach is proposed for computational modelling of the mean particle size of PLGA microspheres and rules extraction from tree-based models. The feature selection leads to revealing chemical descriptor variables which are important in predicting the size of PLGA microspheres. In order to achieve better understanding in the relationships between particle size and formulation characteristics, the surface analysis method and rules extraction procedures were applied.

Pore blocking: An innovative formulation strategy for the design of alcohol resistant multi-particulate dosage forms

In this work calcium stearate (CaSt) multi-particulates loaded with codeine phosphate (COP) were developed in an attempt to provide extended release (ER) combined with alcohol dose dumping (ADD) resistance. The pellets were prepared via wet/extrusion spheronization and ER characteristics were obtained after fluid bed drying at 30°C. Pore blockers (i.e., xanthan, guar gum and TiO2) were integrated to control the uptake of ethanolic media, the CaSt swelling and consequently, the COP release. While all three pore blockers are insoluble in ethanol, xanthan dissolves, guar gum swells and TiO2 does not interact with water. The incorporation of 10 and 15% TiO2 still provided ER characteristics and yielded ADD resistance in up to 40v% ethanol. The in-vitro data were subjected to PK simulations, which revealed similar codeine plasma levels when the medication is used concomitantly with alcoholic beverages. Taken together the in-vitro and in-silico results demonstrate that the incorporation of appropriate pore blockers presents a promising strategy to provide ADD resistance of multi-particulate systems.

Investigation into the Effect of Ethylcellulose Viscosity Variation on the Drug Release of Metoprolol Tartrate and Acetaminophen Extended Release Multiparticulates-Part I.

Ethylcellulose is one of the most commonly used polymers to develop reservoir type extended release multiparticulate dosage forms. For multiparticulate extended release dosage forms, the drug release is typically governed by the properties of the barrier membrane coating. The ICH Pharmaceutical Development Guideline (ICH Q8) requires an understanding of the influence of critical material attributes and critical process parameters on the drug release of a pharmaceutical product. Using this understanding, it is possible to develop robust formulations with consistent drug release characteristics. Critical material attributes for ethylcellulose were evaluated, and polymer molecular weight variation (viscosity) was considered to be the most critical attribute that can impact drug release. To investigate the effect of viscosity variation within the manufacturer's specifications of ethylcellulose, extended release multiparticulate formulations of two model drugs, metoprolol tartrate and acetaminophen, were developed using ETHOCEL™ as the rate controlling polymer. Quality by Design (QbD) samples of ETHOCEL Std. 10, 20, and 100 Premium grades representing the low, medium, and high molecular weight (viscosity) material were organically coated onto drug layered multiparticulates to a 15% weight gain (WG). The drug release was found to be similar (f 2 > 50) for both metoprolol tartrate and acetaminophen multiparticulates at different coating weight gains of ethylcellulose, highlighting consistent and robust drug release performance. The use of ETHOCEL QbD samples also serves as a means to develop multiparticulate dosage formulations according to regulatory guidelines.

Advanced stable lipid-based formulations for a patient-centric product design

Multiparticulate dosage forms are a recent strategy to meet the special needs of children, elderly people and patients suffering from dysphagia. Our study presents a novel and cost-efficient approach for the manufacturing of a taste-masked multiparticulate system with a stable immediate release profile by applying lipid-based excipients in a solvent-free hot melt coating process.The thermosensitive N-acetylcysteine (N-ac) was used as model drug and hot-melt coated with a mixture of tripalmitin and polysorbate 65.A predictive in vitro method for the evaluation of the taste masking efficiency was developed based on the deprotonation of the carboxyl group of N-ac and the decline of pH, responsible for the unpleasant sour taste of the compound. The method was confirmed using in vivo studies. Differential scanning calorimetry and X-ray scattering experiments revealed polymorphic transformation and its dependency on transformation time, temperature and emulsifier concentration. During the process, the coating was transformed almost completely into the stable β-polymorph, leading to an unaltered dissolution profile during storage. A statistical design was conducted that revealed the critical process parameters affecting the taste masking efficiency and drug release.This study shows the successful application of solvent-free hot-melt coating in the development of a taste-masked and stable formulation.

Factors influencing the erosion rate and the drug release kinetics from organogels designed as matrices for oral controlled release of a hydrophobic drug

This article proposes solid-like systems from sunflower oil structured with a fibrillar network built by the assembly of 12-hydroxystearic acid (12-HSA), a gelator molecule for an oil phase. The resulting organogels were studied as oral controlled release formulations for a lipophilic drug, Efavirenz (EFV), dissolved in the oil. The effects of the gelator concentration on the thermal properties of the organogels were studied by Differential Scanning Calorimetry (DSC) and showed that drug incorporation did not change the sol–gel–sol transitions. The erosion and drug release kinetics from organogels under conventional (filling gelatin capsules) or multiparticulate (beads obtained by prilling) dosage forms were measured in simulated gastric and intestinal fluids. EFV release profiles were analyzed using model-dependent (curve-fitting) and independent approaches (Dissolution Efficiency DE). Korsmeyer–Peppas was the best fitting release kinetic model based on the goodness of fit, revealing a release mechanism from organogels loaded with EFV different from the simple drug diffusion release mechanism obtained from oily formulations. From organogels, EFV probably diffuses through an outer gel layer that erodes releasing oil droplets containing dissolved EFV into the aqueous medium.

Prilling as manufacturing technique for multiparticulate lipid/PEG fixed-dose combinations

This study focused on the evaluation of prilling as a technique for the manufacturing of multiparticulate dosage forms. Prills, providing controlled and immediate drug release, were processed and finally combined in capsules yielding a fixed-dose combination. Metoprolol tartrate (MPT) and hydrochlorothiazide (HCT) were used as controlled and immediate release model drugs, respectively. These drugs were embedded in matrices composed of fatty acids and polyethylene glycol (PEG). In order to tailor drug release from the prills, the type of fatty acid, the PEG molecular weight and the fatty acid/PEG ratio were varied. To provide controlled drug release, MPT was embedded in matrices containing PEG and behenic acid. Using different PEG molecular weights (PEG 4000, 6000 and 10,000), MPT release could be tailored over a wide range. To obtain immediate release, HCT was incorporated in matrices composed of PEG and stearic acid. Since high amounts (at least 60%) of PEG were needed for acceptable immediate release, HCT release was independent on PEG molecular weight. Solid state characterization revealed that MPT crystallinity was decreased, while HCT was molecularly dispersed throughout the matrix. Drug release of both MPT and HCT prills was stable during storage. Compared to a fixed-dose reference, oral co-administration of the MPT and HCT prills to dogs yielded a similar bioavailability for the HCT prills, while the MPT prills resulted in a significant higher bioavailability.

Development of papain containing pellets produced by extrusion–spheronization: an operational stage approach

The performance of the standardized extrusion–spheronization technique, operational conditions, formulation parameters and storage of the final product over the bioactivity of papain containing pellets has been evaluated to obtain an insight into the potential of the technique for the manufacture of solid protein formulations. The pellets produced were assayed in terms of biological activity – monitored at each operational stage using N-benzoyl-dl-arginine ρ-nitroanilide as a substrate, and according to the physical properties – evaluated by means of size distribution, apparent density and friability. The produced pellets presented adequate physical and mechanical properties. Monitoring biological activity at each production stage revealed that the most critical steps corresponded to drying and storage, with bioactivity decay ranging from 5 to 30% and 5 to 20% for each process. Dry mixing and extrusion did not hold any influence over papain activity, while wet massing decreased the bioactivity by approximately 0–5% and the spheronization 0–2%. The results varied as a function of the experimental conditions and formulation components. In conclusion, the extrusion--spheronization technique was suitable to produce solid multiparticulate dosage forms for papain, considering the possibility to originate pellets with relatively low bioactivity decay. However, weak points of the technique corresponded to the wet massing and drying stages as well as storage.

Prilling of fatty acids as a continuous process for the development of controlled release multiparticulate dosage forms

In this study, prilling was evaluated as a technique for the development of multiparticulate dosage forms using the fatty acids, stearic acid, and behenic acid as potential matrix formers to control the release of metoprolol tartrate (MPT), a highly water soluble drug. The in vitro drug release was dependent on the drug load, type of fatty acid, and pH of the dissolution medium. Higher drug loads resulted in faster release with behenic acid releasing drug over longer periods relative to stearic acid. The in vitro drug release was pH-dependent at low drug load with the release being slower at lower pH. Due to ionization of the fatty acid at pH 7.4, drug release was susceptible to the ionic strength at this pH value. Solid state characterization indicated that the crystalline state of the fatty acids was not affected by thermal processing via prilling, while the crystallinity of MPT was decreased. During storage, the amorphous MPT fraction recrystallized in the entire matrix. Drug release from behenic acid matrices was increased during storage at 40°C; however, no polymorphism of behenic acid was detected. The bioavailability of MPT, after oral administration to dogs as prills containing 30% and 40% MPT using behenic acid as matrix former, was not significantly different from a commercial sustained release reference formulation, although the 40% MPT prills showed a burst release.

Formulation and Optimisation of Sustained Release Spray-Dried Microspheres of Glipizide Using Natural Polysaccharide

The objective of this study was to investigate the combined influence of three independent variables in the preparation of glipizide microspheres by the spray-drying method. A three factor, three level Box-Behnken design was used to derive polynomial equations and construct response surface plots to predict responses. The independent variables selected were concentration of polymer (xyloglucan) (X1), amount of crosslinking agent (X2), and feed rate (X3). Fifteen batches were prepared and evaluated for percentage drug entrapment and time for 80% drug release (t80). Response surface plots were constructed to demonstrate the combined effects of factors X1, X2, and X3 on response percent entrapment. The optimal microsphere preparations displayed a percent entrapment between 96.96 and 98.11 and a t80 between 420 and 439 min. The microspheres had particle size between 3 and 6 microns, and differential scanning chromatography thermograms showed the presence of glipizide in amorphous form in microspheres. Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as number of small independent subunits. The microspheres as drug delivery systems are especially suitable for providing oral controlled release formulations with low risk of dose dumping, Microspheres can be blended suitably to attain different release patterns. Glipizide is recommended orally for treatment of type II diabetes and is administered in 2 or 3 doses of 2.5 to 10 mg per day. The development of controlled-release dosage form would offer effective control by releasing drug over period of time. The present work describes formulation of microspheres containing glipizide using the tamarind seed polysaccharide or xyloglucan as carrier. The spray-drying method was used to formulate the microspheres and variables (concentration of xyloglucan, amount of crosslinking agent, and feed rate) affecting performance parameters such as time for 80% drug release and percent drug entrapment were optimized using a statistical design (Box Behnken design). The microspheres had particle size between 3 and 6 microns, had entrapment between 97 and 99%, and sustained the drug release beyond 7 hours.