Extended-release Dosage Forms Research Articles

Effect of Omeprazole Administration on the Pharmacokinetics of Oral Extended-Release Nifedipine in Healthy Subjects.

Oral extended-release (ER) dosage forms have been used to sustain blood drug levels, reduce adverse events, and improve patient compliance. We investigated potential effects of comedication on pharmacokinetic exposure of nifedipine ER products with different formulation designs and manufacturing processes. A clinical study compared a generic version of nifedipine ER tablet with pH-dependent dissolution behavior with an osmotic pump product with pH independent drug release under fasting condition. In this study, two nifedipine tablet products were tested with or without short-term omeprazole comedication in healthy subjects. Seven-day administration of omeprazole before nifedipine dosing significantly increased the gastric pH, and subsequently increased the geometric least square (LS) means of area under the concentration-time curve from time zero to the last measurable timepoint (AUC0-t ) and maximum plasma concentration (Cmax ) of nifedipine to 132.6% (90% confidence interval (CI): 120.6-145.7%) and 112.8% (90% CI: 100.8-126.3%) for pH-dependent ER tablets, and 120.6% (90% CI: 109.7-132.5%) and 122.5% (90% CI: 113.7-131.9%) for the pH-independent ER tablets, respectively. Similar extent of increase in AUC0-t and Cmax was confirmed in the subpopulations whose gastric pH was ≥ 4 or ≤ 3 in subjects with or without omeprazole administration. Given that similar increases in drug exposures were observed for both pH-dependent and pH-independent nifedipine formulations and the geometric LS mean ratios were between 112% and 133% with and without short-term omeprazole comedication, the gastric pH may have limited effects on omeprazole-induced nifedipine PK changes on the tested formulations. The inhibition of cytochrome P450 3A4 activity may play a significant role causing nifedipine exposure changes for both formulations, which would warrant additional assessment.

Sphingosomes: A Novel Vesicular Drug Delivery System

Sphingosomes are bilayer vesicles, primarily made of natural or synthetic sphingolipids, that completely surround an aqueous volume. Sphingosomes address the main issues with vesicle systems (liposomes, niosomes), including their lack of stability, short in vivo circulation times, and poor tumour loading efficacy in cancer therapy. Sphingosomes are a promising vesicular drug delivery system that can transport therapeutic chemicals for a variety of potential applications, according to the review's findings. The development of novel medication delivery systems has received a lot of attention in recent decades (NDDS). To begin, it should administer the medication at a pace determined by the body's requirements throughout the course of therapy. Second, it must direct the active entity to the action location. None of these can be met by conventional-dose forms, including extended-release dosage forms. No existing drug delivery system now acts optimally, although genuine efforts have been made to accomplish them via different new drug delivery methods.1-5

A Review on Osmotic Drug Delivery System

Conventional drug delivery systems have slight control over their drug release and nearly uncontrollable over the effective concentration at the target site. This type of dosing pattern might effect on constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled design over a prolonged period of time by the controlled or modified release drug delivery systems. For most of the drugs, oral route is the most tolerable route of administration. Certain molecules may have low oral bioavailability because of solubility or permeability limitations. Evolution of an extended-release dosage form also need sensible absorption throughout the gastro-intestinal tract (GIT). Among the existing techniques to improve the bioavailability of these drugs fabrication of osmotic drug delivery system is the most suitable one. Osmotic drug delivery systems release the drug with the zero-order kinetics at a constant rate. This review brings out advantages, disadvantages, principles, basic components and classification of osmotic drug delivery systems.

Micro-Scale Vacuum Compression Molding as a Predictive Screening Tool of Protein Integrity for Potential Hot-Melt Extrusion Processes.

Hot-melt extrusion (HME) is used for the production of solid protein formulations mainly for two reasons: increased protein stability in solid state and/or long-term release systems (e.g., protein-loaded implants). However, HME requires considerable amounts of material even at small-scale (>2 g batch size). In this study, we introduced vacuum compression molding (VCM) as a predictive screening tool of protein stability for potential HME processing. The focus was to identify appropriate polymeric matrices prior to extrusion and evaluation of protein stability after thermal stress using only a few milligrams of protein. The protein stability of lysozyme, BSA, and human insulin embedded in PEG 20,000, PLGA, or EVA by VCM was investigated by DSC, FT-IR, and SEC. The results from the protein-loaded discs provided important insights into the solid-state stabilizing mechanisms of protein candidates. We demonstrated the successful application of VCM for a set of proteins and polymers, showing, in particular, a high potential for EVA as a polymeric matrix for solid-state stabilization of proteins and the production of extended-release dosage forms. Stable protein-polymer mixtures with sufficient protein stability after VCM could be then introduced to a combination of thermal and shear stress by HME and further investigated with regard to their process-related protein stability.

The Effect of Biorelevant Hydrodynamic Conditions on Drug Dissolution from Extended-Release Tablets in the Dynamic Colon Model.

The in vitro release of theophylline from an extended-release dosage form was studied under different hydrodynamic conditions in a United States Pharmacopoeial (USP) dissolution system II and a bespoke in vitro tubular model of the human colon, the Dynamic Colon Model (DCM). Five biorelevant motility patterns extracted from in vivo data were applied to the DCM, mimicking the human proximal colon under baseline conditions and following stimulation using polyethylene glycol or maltose; these represent the lower and upper bounds of motility normally expected in vivo. In the USPII, tablet dissolution was affected by changing hydrodynamic conditions at different agitation speeds of 25, 50 and 100 rpm. Applying different motility patterns in the DCM affected the dissolution profiles produced, with theophylline release at 24 h ranging from 56.74 ± 2.00% (baseline) to 96.74 ± 9.63% (maltose-stimulated). The concentration profiles of theophylline were markedly localized when measured at different segments of the DCM tube, highlighting the importance of a segmented lumen in intestine models and in generating spatial information to support simple temporal dissolution profiles. The results suggested that the shear stresses invoked by the unstimulated, healthy adult human colon may be lower than those in the USPII at 25 rpm and thus insufficient to achieve total release of a therapeutic compound from a hydroxyethyl cellulose matrix. When operated under stimulated conditions, drug release in the DCM was between that achieved at 25 and 50 rpm in the USPII.

Formulation Development and Release Profile of Levomilnacipran Extended Release Capsules using Principles of Quality by Design

The study’s goal was to use Quality By Design (QbD) principles to design an Extended Release dosage form of levomilnacipran and evaluate its in vitro release profile. Doses of levomilnacipran extended release capsules (LERC) ranging from 20 mg to 120 mg. QbD was employed in this work to design LERC capsule formulation and production, which ensures LERC safety and efficacy. To create the LERC, wurster coating was applied to non-pariel seeds, which were then filled with capsules. To provide prolonged absorption, a polymer derived from ethylcellulose was chosen. Extensive release capsules are made up of four main components: (1) Drug layering, (2) extended release coating, (3) lubricant application, and finally (4) capsule filling. Results revealed that there was no significant difference in release profile LERC in different doses; however, the highest release of drug was seen at 120 mg, that is, 93%. The present formulation may be used as an effective treatment therapy against major depressive disorder.

Preparation and In-vitro Evaluation of Darifenacin HBr as Nanoparticles Prepared as Nanosuspension

Nanosuspension is a term that can be used to describe a colloidal dispersion of nanosized droplets of the drug in an aqueous medium with a size below 1 μm. Drug nanoparticles are one of the most significant methods to reduce the constituent part diameter and increase surface area, improving the dissolution and oral bioavailability of hydrophobic medicines, enhancing drug dissolution rate and bioavailability. Nanoparticles are produced using appropriate techniques for drug delivery applications and administered via various routes, including oral, topical, parenteral, ophthalmic, and pulmonary. Overactive bladder (OAB) affects around 16% of adults and is more common as people become older. It causes a variety of symptoms, including urgency, incontinence, urine frequency, and nocturia. DH. It is newly drug used to treat complicated OAB. It has a higher selectivity for the bladder’s muscarinic receptors. After intravenous and immediate-release oral dose forms. It suffers from extensive first-pass metabolism with a short elimination half-life and ranging between three to four hours). The current research focused on creating an extended-release dosage form utilizing Eudragit RS100. The solvent/anti-solvent precipitation method was used to make darifenacine nanoparticles. A certain quantity of medication was dissolved in a water-miscible solvent (methanol), then poured at a specific speed into water containing stabilizer on a magnetic stirrer for a 1/2-hour; after that, the resulted product was sonicated at 37°C for 15 minutes. The physicochemical interaction among medication with additives was explored utilizing fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetric (DSC). The particle size and zeta potential of the generated nanosuspension were calculated.

Biosynthesized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) as biocompatible microcapsules with extended release for busulfan and montelukast

An extended release dosage form based on encapsulating the challenging drug busulfan within microspheres of the biodegradable, biocompatible and biosynthesized poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) polyester was achieved. The used (PHBV) polymer was biosynthesized by the halophilic archaeon Haloferax mediterranei from date waste biomass as feed-stock. PHBV microspheres of 1.2–2.1 μm diameter were successfully fabricated and loaded with busulfan with an encapsulation efficiency of 29.2 ± 0.2%. In addition, PHBV microspheres of 1.5–3.5 μm diameter and loaded with montelukast sodium (MK) drug were also fabricated with an encapsulation efficiency of 16.0 ± 0.4%. The double-emulsion solvent evaporation method was used to fabricate the drug-loaded microspheres. The drug-loaded microspheres have been characterized by XRD, FTIR and SEM, and confirmed to be successfully fabricated. The drugs in vitro release profiles have shown extended release for up to 3 days in case of busulfan and 8 h in case of montelukast sodium. The in vitro release profiles for busulfan and montelukast suggest that these drug-loaded microcapsules can be efficiently used as new dosage forms to solve the current issues of busulfan administration protocols, and to introduce a new dosage form for montelukast with extended release performance.

Different aspects of polymers – A review article

Polymers play vital roles in the dosage developments of immediate release dosage forms and modified release dosage forms. In different drug delivery systems, polymers are used to develop the dosage forms which are designed to control the release of the therapeutic agent at a constant dose for long time intervals that decrease the cyclic dosages. It is widely used as excipients in formulating various dosage designs to aid the bulk amount so that the drug gets trapped. Immediate-release dosage forms consist of tablets and capsules and modified release dosage forms consist of extended-release dosage forms and gastro retentive release dosage forms. Different modifications are performed with polymers to make conjugates such as polymer-drug and polymer-protein conjugates which are widely used as polymeric carriers in biological applications. Polymers are the backbones of pharmaceuticals drug delivery that are designed to control drugs released through different medical devices such as implants. In biological applications, biodegradable polymers are widely due to having good biocompatibility properties with other therapeutic agents and well-known biodegradability properties. It provides resistance to the drugs from the biological environment and prolongs the drug's release so that it achieves its stability. Different biocompatibility tests are performed in-vivo and in-vitro for both natural as well as synthetic biodegradable polymers that are used in the dosage form and biomedical applications.

Dissolution and Dissolution Test Apparatus: A Review

Dissolution is an official test. These used by pharmacopeias for evaluating drug release of solid and semisolid dosages forms. The application of the dissolution testing ensures consistent product quality and to predict in vivo drug bioavailability. The dissolution test, in its simplest form, placing the formulation in a dissolution apparatus containing suitable dissolution medium, allowing it to dissolved specified period of time and then using appropriate rational method to determine the amount of drug. Dissolution test are probative and analysis like drug degradation profile, shelf-life studies, stability, physical and mechanical testing of dosage forms. The present review outlines findings on various dissolution apparatus, various methods and their modification. Dissolution testing the of various dosage form like Delayed release dosage form, Immediate release dosage form, Extended-release dosage form, Powders, Chewable tablets, Transdermal delivery system, Buccal tablets, Soft gelatin capsule, Chewing gums, Suppositories, Aerosols and others semisolids. This article goal of the description of the all-official dissolution testing apparatus.

Formulation development and in vitro evaluation of bilayer tablets Nicardipine

The present work aims to develop a stable and optimized bilayer dosage form containing immediate release &extended release drug Nicardapine as an extended-release dosage form. A potent calcium channel blocker with marked vasodilator action. It has antihypertensive properties and is effective in the treatment of angina and coronary spasms without showing cardio depressant effects. It has also been used in the treatment of asthma and enhances the action of specific antineoplastic agents. It has a plasma half-life of about (8.6h) and bioavailability is 15-45% orally. For the formulation of Bilayered tablets polymers such as Ethylcellulose, Sodium CMC, CCS, SSG, Magnesium stearate, Talc, PVP-K30, and MCC. Fourier transform Infrared spectroscopy confirmed the absence of any drug/ polymers/ excipients interactions. Preformulation studies were carried out to optimize the ratios required for various Ethylcellulose, Sodium CMC, CCS, SSG, MCC, and PVP-K30. Based on various evaluation parameters formulation M6 (IR) & M6F3 (SR) were selected as optimized formulation. It was observed that Formulations M6 (IR) & M6F3 (SR) gave maximum drug release within time. All formulations were subjected for drug release kinetics studies viz. Zero-order, First order, Higuchi matrix, Peppasmodel equations, and the formulations of floating sustained-release formulations followed the zero-order release with non-fickian diffusion mechanism. Thus conclusion can be made that a stable dosage form can be developed for Nicardapine as immediate release & sustained release by Bilayered tablets.

Drug-related problems of antipsychotics in treating delirium among elderly patients: A real-world observational study.

Delirium is more common and life-threatening among the elderly. Currently, no other medications, including antipsychotics, have been approved for delirium. The number of practice guidelines recommends antipsychotics to be the first option among selected patients. This study aimed to identify the type of drug-related problems (DRPs) concerning antipsychotics use among elderly patients with delirium. A retrospective observational study was conducted by collecting data from 2013 to 2016 in Maharaj Nakorn Chiang Mai Hospital, Thailand. Inpatients who were 60years and over, diagnosed with delirium by ICD-10 diseases coding F05.X and treated with antipsychotics for delirium were included. A modified version of the American Society of Hospital Pharmacists classification criteria (mASHP-delirium) was used. A total of 379 patients were enrolled. Mean daily dose of haloperidol (oral) was 1.06±1.33mg, haloperidol (intramuscular) 2.71±1.88mg, haloperidol (intravenous; IV) 3.42±1.97mg, risperidone was 0.71±0.52mg, and quetiapine was 19.26±15.63mg. Among all, 427 events were classified as DRPs. The most common DRPs included inappropriate duration, dose, route of administration or dosage form accounting for the 416 events (97.4%), followed by actual adverse drug reactions (extrapyramidal symptoms; EPS), 6 events (1.4%) and potential drug-drug interactions for 5 events (1.2%). Of those 416 events, 200 events (48.1%) antipsychotics were continued after discharge and continued for more than 10days. Dosage exceeding initial dose or maximum daily dose accounted for 179 events (43.0%). Other DRPs such as inappropriate route haloperidol IV and receiving the extended-release dosage form of quetiapine involve 26 (6.3%) and 11 (2.6%) events, respectively. To the best of our knowledge, this is the first study using mASHP-delirium to identify DRPs of antipsychotics in treating delirium among elderly patients. Several DRPs were found that might lead to severe adverse drug reactions, particularly EPS and QTc interval prolongation. However, all DRPs could be prevented by developing antipsychotic setting protocols and specialty consulting systems to communicate among healthcare providers caring for vulnerable groups of patients. In addition, a prospective pharmacist intervention is required.

Screening of Bioequivalent Extended-Release Formulations for Metformin by Principal Component Analysis and Convolution-Based IVIVC Approach.

Bioequivalence (BE) is usually hard to achieve for extended-release (ER) dosage form products due to not only its complicated formulation but also to the BCS classification of the investigated drugs. Considering the difficulties in establishing full-scale IVIVC and limited in vivo pharmacokinetics data in the early stage of formulation development, we have selected BCS III drug metformin as a model drug to demonstrate a novel approach for the selection of BE formulations. Firstly, dissolution tests in both standard and biorelevant media were performed followed by identification of the most similar formulation WM to the reference product (GXR) based on principal component analysis (PCA) of the dissolution data. Then, we developed an IVIVC model using the reported GXR pharmacokinetics profiles via a convolution-based approach. Based on our established IVIVC and in vitro dissolution profiles of generic metformin ER products, we were able to predict their in vivo pharmacokinetic profiles and quantitatively compare the differences in AUC and Cmax to ensure the correct selection of BE product. Finally, the selection of WM as the BE formulation of GXR was confirmed with a pilot BE study in healthy volunteers under fasting state. Moreover, the in vivo data from the fed state study were further integrated into our IVIVC model to identify FeSSIF-V2 as the biorelevant media for WM. Our novel integrative approach of PCA with a convolution-based IVIVC was successfully adopted for the screening of the BE metformin ER formulation and such an approach could be further utilized for the effective selection of BE formulation for other drugs/formulations with complex in vivo absorption processes.

Gliclazide: Biopharmaceutics Characteristics to Discuss the Biowaiver of Immediate and Extended Release Tablets

The lists of essential medicines of the World Health Organization (WHO) and Brazil include gliclazide as an alternative to the oral antidiabetic drug of first choice, metformin, in the treatment of type 2 diabetes mellitus because of its pharmacokinetic profile and few side effects. Thus, it is also considered by WHO and the International Pharmaceutical Federation (FIP) as a drug candidate to biowaiver, which is the evaluation of how favorable the biopharmaceutics characteristics are in order to obtain waiver from the relative bioavailability/bioequivalence (RB/BE) studies to register new medicines. This paper presents a review about the solubility, permeability and dissolution of gliclazide. A critical analysis of the information allowed to identify gliclazide as a Biopharmaceutics Classification System (BCS) Class II drug. Therefore, new drugs in immediate release dosage forms will not be eligible for biowaiver. Regarding the extended release dosage forms, besides the limited solubility, no information on the comparative dissolution profile was found, which would be necessary to analyze a possible biowaiver for a smaller dosage. It can be concluded that the registration of new medicines containing gliclazide must undergo RB/BE studies, since there is not enough evidence to recommend the replacement and waiver of such studies for immediate and extended release formulations.

Formulation and evaluation of new oxycodone extended release multiple unit pellet system

Abstract The goal of the present study is to prepare a stable, multiple-unit, extended-release dosage form containing oxycodone pellets coated with aqueous ethylcellulose (EC) dispersion, Surelease E-7-19050. The application of 18% w/w of EC leads to the similar drug release with the hydrophobic, non-swelling, matrix reference product containing 20 mg of oxycodone. Increasing the compression force to 9 kN and including more than 50% w/w of oxycodone pellets into the formulation resulted in faster drug release, indicating the damaging to the EC film coating. The physical appearance of the final formulation, assay of oxycodone, moisture content, and dissolution data over the stability period showed that the multiple-unit pellet system (MUPS) is efficient for the production of highly stable product.

SPLIT-HALF TABLETS: A COMPLETE REVIEW FOR ANALYTICAL TESTING

A solid oral dosage form (as a tablet) which is an immediate or extended-release dosage form which necessitates the scoring bisect of the tablet. This review discusses the quality attributes and interpretations for the split studies of the various tablet formulations using the analytical techniques. Each method of analysis for the evaluation of split-half tablets in terms of its critical quality attributes discusses in detail explanation of analytical methodology and challenges in formulation development. The results for quantitative analytical evaluation in terms of finished product/stability testing and release of the split-half drug product against the acceptance criterion and also discusses the flowchart guidance for the investigation of out of specification results. The present article provides an insight into the complete analytical evaluation of split-half drug product testing according to the requirements of tablet scoring as per US food and drug administration.

HYDROXYAPATITE - CARBON NANOTUBE COMPOSITES FOR DRUG DELIVERY APPLICATIONS

Abstract The aim of this study was the synthesis of composites containing hydroxyapatite (Hap) or silicon substituted hydroxyapatite (HapSi), carboxyl functionalized carbon nanotubes (fMWCNT) and gelatin (G) in different ratios. Ibuprofen (IBU) was chosen as a model drug for the formulation of extended-release dosage forms. The obtained composites were characterized using X-ray diffraction, laser diffraction particle size analyzer, Brunauer-Emmett-Teller surface area measurements, transmission electron microscopy and Fourier transformed infrared spectroscopy. IBU adsorption and desorption was monitored by UV-VIS spectroscopy. The obtained results revealed that composites containing three components exhibit higher adsorption efficiency (Hap-fMWCNT-20G - 82.7% and HapSi-fMWCNT-20G - 84.6%) and extended-release of IBU, due to the chemical bonds between the carboxyl groups of IBU and the functional groups on the composite surface. The adsorption capacity of Hap composites is important for dental or orthopedic implants, the anti-inflammatory substances being adsorbed on their surface; but the adsorption capacity also enhances new bone formation (osteosynthesis) around the implants. These composites are thus attractive materials to be used in bone tissue engineering and drug delivery systems.

Effects of Dissolution Medium pH and Simulated Gastrointestinal Contraction on Drug Release From Nifedipine Extended-Release Tablets*

In contrast to nifedipine matrix-based extended-release dosage forms, the osmotic pump drug delivery systems have a zero-order drug release independent of external variables such as pH, agitation rate, and dissolution media. The objective of this study focuses on the in vitro evaluation of the mechanical properties of osmotic pump and polymer matrix-based formulations in dissolution media, and the potential impacts that media pH and simulated gastrointestinal contraction have on drug release. Two strengths of osmotic pump product A and polymer matrix-based product B were used in this study. An in-house system was developed with the capability of applying mechanical compression and monitoring mechanical properties of sample during dissolution testing. A United States Pharmacopeia or an in-house apparatus was used for dissolution testing under various conditions. Compared to the product A, the mechanical properties of the product B change significantly at various pHs and mechanical compressions. The results suggest that polymer matrix-based products bear a risk of formulation-related interactions with the gastrointestinal tract during in vivo drug dissolution, especially in the case of concomitant pH and gastric contractile changes. Modified dissolution testing devices may help formulation scientists in product development and provide regulatory agencies with an additional metric for quality assurance of drug products.

Extended tacrolimus release via the combination of lipid-based solid dispersion and HPMC hydrogel matrix tablets

The objective of this study is to evaluate the feasibility of obtaining extended release of tacrolimus by a novel combination of lipid-based solid dispersion and matrix-type extended release tablet techniques. Tacrolimus solid dispersion was prepared using glycerylbehenate (Compritol® ATO888) and Pluronic F127 as the carrier materials with hot-melt method, which was then blended with hydrogel matrix materials, such as HPMC and lactose, the powders were directly compressed into tablets. In vitro drug release tests were carried out to evaluate the performance of the solid dispersions and the tablets. The dissolution rate of tacrolimus was significantly improved by the lipid-based solid dispersion, and the incorporation of HPC into the solid dispersion obviously improved its stability after storage. Extended release tablets loaded with tacrolimus solid dispersion showed prolonged drug release patterns over 24 h, the release patterns of the tablets can be tailored by the compositions of the matrix materials, including the types and content of HPMCs. A modified processing method that directly mixed the melted solid dispersion with HPMC powders improved the uniformity of the solid dispersion inside the tablet matrix and release profile. The release data of the extended release tablet fitted well to the Korsmeyer–Peppas model with n value of 0.85, which suggested diffusion- and erosion-controlled release mechanism. The combination of lipid-based solid dispersion and HPMC hydrogel matrix may find wide applications in the extended release dosage forms of high potent, water-insoluble drugs.

Extended release delivery system of metoprolol succinate using hot-melt extrusion: effect of release modifier on methacrylic acid copolymer.

The current study reports on the manufacturing of extended release dosage forms of metoprolol succinate via hot-melt extrusion (HME) technology. Either Eudragit®S100 and Eudragit®L100 alone or in combination with release modifying agent Polyox™ WSR 303 and Eudragit®L100-55 were processed to obtain complete and faster release. Metoprolol succinate with similar solubility parameters to polymer was dispersed in polymer matrix and was characterized by Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), X-ray diffraction (XRD), and scanning electron microscopy (SEM). Stability of drug after extrusion was confirmed by thermogravimetric analysis and high-performance liquid chromatography. Physical characterization method exhibited that the drug was homogeneously dispersed in non-crystalline state in Eudragit®L100-55-based formulations whereas in semi-crystalline state in Polyox™ WSR 303. The drug release percentage was below 3 and 40% in 0.1N HCL with Eudragit®L100-55- and Polyox™ WSR 303-containing formulations, respectively, and exhibited pH-dependent dissolution properties. The drug-release mechanism was anomalous with Polyox™ WSR 303 formulations whereas diffusion through pore formation was obtained with Eudragit®L100-55. Both Eudragit®L100-55 and Polyox™ WSR 303 changed the release mechanism and kinetics of drug release from thermally processed dosage forms. The optimized stable formulation is similar to the marketed formulation with F2 value of 72.36. Thus, it can be concluded that HME was exploited as an effective process for the preparation of controlled release matrix system based on pH-dependent polymer matrices Eudragit®S100 and Eudragit®L100.