Target Release Profile Research Articles

Smart Polymer Systems: A Futuristic Approach to Enhance Therapeutic Efficacy

Abstract: Recently, pharmaceutical industries have placed considerable emphasis on formulating drug delivery systems that precisely target specific sites, optimize drug utilization, minimize excipient usage, and mitigate side effects. Smart polymers hold tremendous promise in the design of innovative formulations tailored to deliver drugs with enhanced precision, efficacy, and therapeutic benefits while minimizing adverse effects. Within drug delivery, smart polymers demonstrate exceptional potential in achieving controlled and targeted release profiles, ensuring drug delivery to specific receptors, and minimizing offtarget effects. This comprehensive review article focuses on the latest developments in smart polymers, primarily in the domains of drug delivery. By intelligently responding to external stimuli, smart polymer-based materials offer various applications, making them pivotal in modern pharmaceutical research. By utilizing the remarkable attributes of smart polymers, researchers and industry stakeholders can forge a path toward personalized, efficient, and patient-centric therapies with reduced side effects, propelling the pharmaceutical field into an era of unprecedented advancements.

Research on Formulation and Evaluation of Floating Microspheres

The purpose of this study is to design and evaluate a floating multipart oral delivery system for diltiazem hydrochloride that can provide sustained release. The aim of the work is also to study various parameters that influence the behaviour of floating multiparticles in an oral dosage form. Floating microspheres were prepared by a non-aqueous emulsifying solvent evaporation technique using ethyl cellulose and Eudragit RS-100 asthe rate-controlling polymer. In vitro activity was evaluated using standard pharmacopoeia and other tests such as drug-polymer compatibility, (%)yield, particle size analysis, drug entrapment efficiency, surface topography, in vitro buoyancy and release studies. The results show that the mixing ratio of the components in the organic phase affected the size, size distribution (199-320 µm), drug concentration(59-84%), percent yield (57-77%) and drug. Liberation microsphere (45-99aftern12 hours) and swimming time > 12 hours. The best results were obtained in the ratio drug: polymer Eudragit RS-100 (1:3). Good in vitro floating behaviour was observed in most cases, and various drug release patterns could be achieved by varying the polymer ratio, which was optimized to match the target release profile. Stability studies showed no significant change in the drug content of the formulation even after 3months. The data obtained in this study therefore suggest a floating dose of micro particles

Scaling up and evaluation of Dyphylline controlled release matrix tablets

The aim of the current study was to scale up controlled release matrix tablets of Dyphylline, used for the management of various respiratory conditions such as asthma, cardiac dyspnea, chronic bronchitis, and emphysema. The tablets were scaled up to 3500 tablets scale then the optimized formulations were further scaled up to 35000 tablets. Tablets were manufactured using direct compression, wet granulation, and hot melt methods. The prepared tablets were evaluated for Hardness, Friability, content uniformity, in-vitro drug release, and stability study. The results obtained showed that the ten prepared tablets showed accepted values for the hardness, friability, and content uniformity tests. The formulations showed controlled drug release profiles with high similarity to our target release profile (f values ranged from 63.9 to 84.9). The release profiles showed a better fit to zero order than diffusion model. The Exponent n of Korsmeyer-Peppas model ranged from 0.67 to 0.692 indicating non-Fickian diffusion. The stability study indicating good stability of the selected formulation. All these results concluded that formulation prepared by wet granulation can be manufactured on large scale perfectly.

Duocapsule and alternative shell material to gelatin: Advancement in capsule formulation

Owing to broad advantages like self-medication, unit dosage form, and patient compliance, cost effective, limited interaction with the excipients and possibility of mask the unpleasant taste, capsules are the most extensively recognized conventional solid dosage form after Tablet. In the world of Novel drug delivery system to overcome the disadvantages of conventional delivery system modifications are made in the capsule to develop a product of higher selectivity for medical treatment like the capsules that facilitates the controlled drug delivery, sustained and targeted release profiles with its own benefits as conventional dosage form. The advancement in capsules has led to the formation of different types of capsule formulations such as tablets in capsules, pellets in capsule and the capsule in another capsule, liquid in capsule products and pellets in capsule formulations. This article aims to highlights the advancement in the capsule system, particularly Duocapsules and capsules with capsule shell prepared with alternative shell material to gelatin. The Duo capsule is also called as capsule in capsule formulation as it contains two capsules one with the bigger size containing the smaller sized capsule inside it with different or same formulations in various forms such as liquids, solids, powders, tablets, pellets etc. The article mainly focuses on the different applications, advantages, formulation consideration, and applicable drugs of duo capsules. Considering the challenges invovled in manufacturing the gelatin shell and unstability of in different climatic conditions, the present article also emphasizes on the formulation development in capsule system with alternative polymers to the gelatin like HPMC, starch and PVA copolymer capsule shells.

Model-Informed drug development of gastroretentive release systems for sildenafil citrate

Gastroretentive drug delivery systems (GRDDS) are modified-release dosage forms designed to prolong their residence time in the upper gastrointestinal tract, where some drugs are preferentially absorbed, and increase the drug bioavailability. This work aimed the development of a novel GRDDS containing 60 mg of sildenafil citrate, and the evaluation of the feasibility of the proposed formulation for use in the treatment of pulmonary arterial hypertension (PAH), for once a day administration, by using in silico pharmacokinetic (PK) modeling and simulations using GastroPlusTM. The Model-Informed Drug Development (MIDD) approach was used in formulation design and pharmacokinetic exposure prospecting. A 22 factorial design with a central point was used for optimization of the formulation, which was produced by direct compression and characterized by some tests, including buoyancy test, assay, impurities, and in vitro dissolution. A compartmental PK model was built using the GatroPlusTM software for virtual bioequivalence of the proposed formulations in comparison with the defined target release profile provided by an immediate release (IR) tablet formulation containing 20 mg of sildenafil administered three times a day (TID). The results of the factorial design showed a direct correlation between the dissolution rate and the amount of hydroxypropyl methyl cellulose (HPMC) in the formulations. By comparing the PK parameters predicted by the virtual bioequivalence, the formulations F1, F2, F3 and F5 failed on bioequivalence. The F4 showed bioequivalence to the reference and was considered the viable formulation to substitute the IR. Thus, GRDDS could be a promising alternative for controlling the release of drugs with a pH-dependent solubility and narrow absorption window, specifically in the gastric environment, and an interesting way to reduce dose frequency and increase the drug bioavailability. The MIDD approach increases the level of information about the pharmaceutical product and guide the drug development for more assertive ways.

Reservoir-Style Polymeric Drug Delivery Systems: Empirical and Predictive Models for Implant Design.

Controlled drug delivery systems can provide sustained release profiles, favorable pharmacokinetics, and improved patient adherence. Here, a reservoir-style implant comprising a biodegradable polymer, poly(ε-caprolactone) (PCL), was developed to deliver drugs subcutaneously. This work addresses a key challenge when designing these implantable drug delivery systems, namely the accurate prediction of drug release profiles when using different formulations or form factors of the implant. The ability to model and predict the release behavior of drugs from an implant based on their physicochemical properties enables rational design and optimization without extensive and laborious in vitro testing. By leveraging experimental observations, we propose a mathematical model that predicts the empirical parameters describing the drug diffusion and partitioning processes based on the physicochemical properties of the drug. We demonstrate that the model enables an adequate fit predicting empirical parameters close to experimental values for various drugs. The model was further used to predict the release performance of new drug formulations from the implant, which aligned with experimental results for implants exhibiting zero-order release kinetics. Thus, the proposed empirical models provide useful tools to inform the implant design to achieve a target release profile.

Development and Evaluation of Gastro Retentive Floating Drug Delivery System of Ondansetron Hydrochloride

The Aim of the present study was to develop & evaluate Gastro-retentive floating Tablet of Ondansetron hydrochloride. The Objective was to calibrate and validate the UV- spectroscopy analytical method and to prepare and optimize the GR Floating tablets of Ondansetron hydrochloride in terms of dissolution release profile. The FDDS of the drug can minimize the fluctuation of drug plasma levels and result to associated adverse reactions, dosing frequency, and improved patient compliance. Conventionally, Ondansetron hydrochloride is taken up 2-3 times daily in the treatment of nausea and vomiting. Gastro retentive floating tablet of Ondansetron hydrochloride is better suited for treatment of postoperative nausea vomiting. In the present study, nine Gastro retentive Floating tablet formulations (F1, F2.....F9) of Ondansetron hydrochloride were prepared by the method of direct compression and polymers HPMC K15 were used and Guargum and Chitosan, in different quantity to normalise their effect on the’ release profile of drug . Target release profile was >80% release of drug in 12 hours. Tablets were evaluated for various parameters namely: thickness, weight variation’, friability, hardness, assay, in-vitro buoyancy study & drug release. Formulation F8 containing Chitosan (26.66% w/w), Guargum (26.66% w/w) and Sod. Carbonate (25.83% w/w) had the desirable release profile.
 Keywords: Ondansetron hydrochloride; Gastro retentive floating tablet, Chitosan, Guar gum, Drug release

Mathematical modelling of drug release from a porous granule

Understanding drug release from pharmaceutical granules is vital to the development of targeted release profiles. A model describing diffusion and solubility-limited drug dissolution and release from a porous spherical granule of drug and excipient is considered. Radially varying porosity and initial concentration profiles which can arise in pharmaceutical granules are incorporated. A range of boundary-value and moving-boundary-value problems arise, depending on the relationship between the drug saturation concentration in the solvent medium and the initial drug concentration and porosity profiles. The model is derived in detail for the case where the initial drug concentration is greater than the drug saturation concentration in all parts of the granule. In this case, a moving boundary forms at the granule surface and propagates inwards, separating an unextracted inner core from a shell region which undergoes extraction via diffusion. The full model is non-dimensionalised and analysed using asymptotic methods and numerical solution. A leading-order model is derived by exploiting a small parameter corresponding to the ratio of the drug saturation concentration to the maximum initial concentration in the granule, allowing estimation of the time taken for the moving boundary to reach the granule centre. The behaviour of the full model is considered by solving it using a boundary immobilisation method and the finite element method for a range of parameters and comparing to the leading-order model. Finally, the model outputs for the moving boundary position and normalised drug release are compared with experimental data from the literature.

Pharmaceutical Product Modularization as a Mass Customization Strategy to Increase Patient Benefit Cost-Efficiently

Customized pharmaceutical products aim to comply with the individual needs of a patient to enhance the treatment outcome. The current pharmaceutical production paradigm is, however, dominated by mass production, where the pharmaceutical products embrace a one-size-fits-all design with a low possibility of treatment optimization to patient needs. This production paradigm is not designed or intended for customized pharmaceutical products and operating this production context for customized pharmaceutical products is argued to be cost-inefficient. To address this challenge of inefficient production of customized pharmaceutical products, this study proposes an approach to modular pharmaceutical product design. As a mass customization strategy, product modularization enables serving customers with customized products cost-efficiently. The proposed modular pharmaceutical products integrate three product design requirements originating from patient needs: a scalable dose strength, a flexible target release profile, and a scalable treatment size. An approach to assess the value of these product designs is presented, by means of proposing three benefit metrics complying with respective design requirements and a cost metric assessing the cost of producing these modular pharmaceutical product designs. Results suggest that pharmaceutical product modularization can, by keeping the number of produced components low, substantially increase the external product variety and, hence, enhance the treatment outcome of patients. Furthermore, results indicate that the achieved benefit for the patient through product modularization increases beyond additional costs arising during production. However, a careful modularization must be performed to optimize the tradeoff between the increased benefit and cost.

Formulation and Evaluation by Appling 32 (Three Squire) Factorial Design of Lercanidipine Hydrochloride Buccal Tablets with Mucoadhesive Polymers

Abstract: Aim: The aim of the present research work is to develop buccal tablets of Lercanidipine hydrochloride to reduce dosage frequency; obtain optimized and controlled therapy, better patient compliance. Materials and Methods: Lercanidipine HCL was obtained as a gift sample from Sun Pharma, Baroda, India. Other ingredients like Na-alginate, Carbopol 934 P, Micro Crystalline Cellulose, Mannitol, Magnesium stearate, Ethyl cellulose and Hydroxy Propyl Methyl CelluloseK4M were purchased from various sources. All other ingredients used were of analytical grade. Attempt was made by using mucoadhesive polymers HPMC K4 M, sodium alginate and carbopol 934 P in combination with Ethyl Cellulose as an impermeable backing layer. Results: Combination of polymer HPMC K4 M and sodium alginate release of drug was found in desired manner than other combinations. On the basis of the preliminary trials a 32 full factorial design was employed to study the effect of independent variables such as concentration of sodium alginate: HPMC K4M (X1) and type of filler (X2) on dependent variables. Factorial batches of F1 to F9 were formulated. HPMC K4M exhibited a much greater sustained effect on the release rate compared with sodium alginate. F4 shown the highest f2 value 70.46 and also all the h drug release was within the specified range. Based on the f2 value and targeted release profile the F4 batch was considered as optimized batch. Formulation F4 was subjected to an in vitro buccal permeation study. The results showed drug permeation of 99.04% in 12 h. The correlation between in vitro drug release rate and in vitro drug permeation across the chicken mucosa was found to be positive, with a correlation coefficient (R2) of 0.9921. Conclusion: From kinetic modelling of the dissolution profile of the optimized formulation, it was concluded that there is erosion-controlled release of Lercanidipine from the buccal adhesive drug delivery system. Key words: Lercanidipine hydrochloride, Buccal tablets, HPMC K4M, Buccal permeation study, Erosion controlled release.

Design and Invitro Evaluation of Olmesartan Medoxomil Floating Tablets

The present study aimed to develop controlled release Floating Drug Delivery System (FDDS), which will remain in stomach for longer time while controlling drug release to achieve target release profile using a combination of Hydroxy Propyl Methyl Cellulose of different grades and Carbopol, Hydroxy Propyl Cellulose as Polymer. Olmesartan is an antihypertensive agent which belongs to the class angiotensin II receptor antagonists. Olmesartan medoxomil is a pro-drug that is converted to the active metabolite olmesartan in gastric region (Olmesartan medoxomil is rapidly and completely bioactivated by ester hydrolysis to olmesartan during absorption from the gastrointestinal tract). Olmesartan does not undergo further metabolism and does not interact with cytochrome P450 (CYP) enzymes. Hence we should perform the floating tablets of Olmesartan. The only adverse effect that occurred in >1% of patients treated with it. Therefore, reduction of side effects of olmesartan while prolonging its action by using controlled oral dosage forms is highly desirable. The floating tablets were evaluated for their hardness, friability, drug content, invitro buoyancy, invitro dissolution, swelling and stability studies.

Colon targeting of celecoxib nanomixed micelles using pulsatile drug delivery systems for the prevention of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a debilitating condition characterized by chronic inflammation of the colon which can increase the risk of colon cancer. Celecoxib (CXB), a cyclooxygenase-2 inhibitor, showed potential for the prophylaxis against IBD. However, it suffers from poor aqueous solubility and cardiovascular toxicity on prolonged use. Here, CXB solubility was enhanced using nanomixed micelles (NMMs) and then colon targeted in a pulsatile system to minimize systemic side effects. Pluronic P123 NMMs with bile salts or hydrophilic Pluronics were prepared using the thin film hydration technique. NMMs were characterized for particle size, size distribution and zeta potential before and after freeze drying and for solubility enhancement. The freeze dried NMMs were then loaded in pulsatile systems with varying tablet plugs containing time-dependent polymers at different concentrations. The optimum NMM consisted of Pluronic P123 and sodium taurocholate (1:1) and CXB:surfactant mixture ratio of 1:30. The pulsatile capsules, containing a tablet plug made of 75% Carbopol®, achieved the target release profile with 88.35% of the dose released after an 8 hrs lag period. Finally, the optimum NMM/pulsatile system showed protective effect against experimentally-induced colitis compared to conventional capsules and pulsatile capsules filled with pure CXB.

Formulation and evaluation of almotriptan controlled release pellets

Abstract: The aim of the present study was to formulate and evaluate Almotriptan pellets. Almotriptan controlled release pellets were prepared by Solution layering technique by using croscarmellose and povidone in former case and three different polymers HPMC K 100, Ethyl cellulose and Eudragit RS 100 as rate controlling polymer in three different ratios like 1:1, 1:1.5 and 1:2 to achieve desired release in later case. Evaluation was performed according to the Pharmacopoeia standards including Drug excipients compatibility, Percentage yield, Particle size distribution, Drug content analysis and in-vitro release study. The best results were found to be using Almotriptan and Eudragit RS 100 in 1:2 ratios. A broad variety of drug release pattern could be achieved by variation of polymers ratios which was optimized to match the target release profile. In comparison of in-vitro release studies for different controlled release formulations, F9 releases 98.54% of drug at the end of 12th hour and was considered as best formulation. Stability study has shown no significant change in the drug content analysis and in-vitro dissolution study of best formulation even after 6 months.
 Keywords: Almotriptan, Controlled release, Dissolution profile, in-vitro drug release, Stability studies.

Development, Evaluation and Optimization of Osmotic Controlled Tablets of Aceclofenac for Rheumatoid Arthritis Management

Objective: Rheumatoid arthritis is a dreaded disease, characterized by pain, inflammation and stiffness of joints, leading to severe immobility problems. The disease shows circadian variation and usually gets aggravated in early morning hours. Aceclofenac, a BCS Class II compound is routinely used in the treatment of pain and inflammation associated with rheumatoid arthritis. The objective of this study was to develop an osmotic delivery system of Aceclofenac that after administration at bedtime would deliver the drug in the morning hours. </P><P> Methods: A series of osmotically controlled systems of aceclofenac was developed by using lactose, sodium chloride and hydroxypropyl methylcellulose K100M as osmogens. Cellulose acetate (2% w/v in acetone) with varying concentrations of polyethylene glycol-400 was used as the coating polymer to create semi permeable membrane and dissolution was carried out in 290 mOsm phosphate buffer. Formulation optimization was done from four considerations: cumulative release at the end of 6 hours (lag time), cumulative release at the end of 7 hours (burst time), steady state release rate and completeness of drug release. </P><P> Results: A formulation having swelling polymer hydroxypropyl methylcellulose in the core and lactose and sodium chloride as osmogens, polyethylene glycol-400 (16.39 %) as pore former, with a coating weight of 5% was a close fit to the target release profile and was chosen as the optimum formulation. Conclusion: Aceclofenac tablets containing lactose, HPMC and sodium chloride in the core, given a coating of cellulose acetate and PEG-400 (5% wt gain), generated a release profile for optimum management of rheumatoid arthritic pain.

Dual-Sensitive Hydrogel Nanoparticles Based on Conjugated Thermoresponsive Copolymers and Protein Filaments for Triggerable Drug Delivery.

In this study, novel hydrogel nanoparticles with dual triggerable release properties based on fibrous structural proteins (keratin) and thermoresponsive copolymers (Pluronic) are introduced. Nanoparticles were used for curcumin delivery as effective and safe anticancer agents, the hydrophobicity of which has limited their clinical applications. A drug was loaded into hydrogel nanoparticles by a single-step nanoprecipitation method. The drug-loaded nanoparticles had an average diameter of 165 and 66 nm at 25 and 37 °C, respectively. It was shown that the drug loading efficiency could be enhanced through crosslinking of the disulfide bonds in keratin. Crosslinking provided a targeted release profile under reductive conditions using an in vivo agent, glutathione (GSH), or in the presence of trypsin. Cytocompatibility assay using HeLa and L929 fibroblast cells exhibited no adverse effect of nanoparticles on cell viability up to 1 mg/mL. Besides, the green fluorescence of curcumin confirmed the uptake of drug-loaded nanoparticles by cancer cells. The redox and temperature-sensitive nanoparticles are potentially useable for the efficient delivery of hydrophobic drugs to targeted regions having a triggerable release profile.

Formulation and Development of a Compression coated, matrix based, tablet of Verapamil HCl using design of experiments

Compression coating provides a unique platform for formulating modified release products in a way the dosage form can successfully be targeted to localize the release of the drug in any desired portion of the GIT without the additional step of film coating. The current work focuses on the development and optimization of modified release Verapamil Hydrochloride tablets using compression coating. The effect of various concentrations of different grades HPMC polymers, like, K4M, K15M and K100M on the release profile was studied in DOE environment. The results of the DOE provide an optimized range of the three polymers which could potentially give the targeted release profile for all drugs which have solubility profiles similar to Verapamil HCl. Three batches of optimized formulation were loaded on to accelerated stability studies at 40°C/75% RH in HDPE containers and the 3 months stability data indicates that there is no significant change in either the potency of the dosage form or its in vitro dissolution profile.

Formulation and evaluation of metformin HCl floating microspheres

The purpose of the present investigation was the preparation and evaluation of gastro-retentive floating drug delivery system for anti-diabetic drug metformin hydrochloride that would retain the drug in stomach and continuously release the drug in controlled manner up to a predetermined time leading to improve bioavailability. The microspheres were prepared by oil-in-oil emulsion solvent evaporation technique using ethyl cellulose, methacrylic acid copolymer (Eudragit RS100, Eudragit RSPO and Eudragit RLPO). The dried floating microspheres were evaluated for percentage yield (%), actul drug content (%), drug entrapment efficiency, floating behavior, scanning electron microscopy and in vitro drug release studies. The microspheres were found spherical, porous and free flowing with a size range. Compatibility studies were performed by fourier transform infra-redand (FTIR) and differential thermal analysis (DTA) techniques. The DTA and FTIR data stated that drug and excipient were compatible. In-vitro release kinetics were studied in different mathematical release models following the zero order, Higuchi and Korsemeyer to find out the linear relationship and release rate of drug. The drug might be released by both diffusion and erosion as the correlation coefficient (R2) best fitted with Korsemeyer model and release exponent (n) was 0.45-0.89. In most cases good in vitro floating behavior was observed and a broad variety of drug release pattern was achieved by variation of the polymer which optimized to match target release profile. The developed floating microspheres of metformin hydrochloride may be used in clinic for prolonged drug release in stomach for at least 8 hrs, thereby improving the bioavailability and patient compliance.Asian J. Med. Biol. Res. December 2015, 1(3): 396-405

Formulation and In Vitro and In Vivo Evaluation of Lipid-Based Terbutaline Sulphate Bi-layer Tablets for Once-Daily Administration

The objective of this study was to prepare and evaluate terbutaline sulphate (TBS) bi-layer tablets for once-daily administration. The bi-layer tablets consisted of an immediate-release layer and a sustained-release layer containing 5 and 10mg TBS, respectively. The sustained-release layer was developed by using Compritol®888 ATO, Precirol® ATO 5, stearic acid, and tristearin, separately, as slowly eroding lipid matrices. A full 4 × 2(2) factorial design was employed for optimization of the sustained-release layer and to explore the effect of lipid type (X 1), drug-lipid ratio (X 2), and filler type (X 3) on the percentage drug released at 8, 12, and 24h (Y 1, Y 2, and Y 3) as dependent variables. Sixteen TBS sustained-release matrices (F1-F16) were prepared by melt solid dispersion method. None of the prepared matrices achieved the targeted release profile. However, F2 that showed a relatively promising drug release was subjected to trial and error optimization for the filler composition to develop two optimized matrices (F17 and F18). F18 which consisted of drug-Compritol®888 ATO at ratio (1:6 w/w) and Avicel PH 101/dibasic calcium phosphate mixture of 2:1 (w/w) was selected as sustained-release layer. TBS bi-layer tablets were evaluated for their physical properties, in vitro drug release, effect of storage on drug content, and in vivo performance in rabbits. The bi-layer tablets showed acceptable physical properties and release characteristics. In vivo absorption in rabbits revealed initial high TBS plasma levels followed by sustained levels over 24h compared to immediate-release tablets.

DESIGN, OPTIMIZATION, DEVELOPMENT AND EVALUATION OF ONCE A DAY CONTROLLED RELEASE FORMULATION OF RIVASTIGMINE TARTARATE

Rivastigmine, an Anti-Alzheimer’s drug suffer from a major limitation of sever GI adverse events such as nausea, vomiting, diarrhea, loss of appetite, weight loss and increase dosing frequency [1]. The present work aim at design, optimization and development of rivastigmine once a day controlled release formulation to minimize the above limitation and increase patient’s compliance. Based on the target in-vitro release profile derived from pharmacokinetic simulation [2], a once a day matrix tablet with the simulated dose was developed. The simple direct compression process was followed as a manufacturing process, the percentage of Polymer HPMC K100M, Polyethylene oxide (PEO WSR303) and insoluble excipients microcrystalline cellulose used in the formulation were optimized using 23 full factorial design. The formulations were then evaluated for the physical characteristics of blend, tablets, swelling index, percentage of erosion, drug release and release rate kinetic. The quadratic model was suggested, contour and 3D graphs were generated. The optimized formulation was subjected to stability studies. The final optimized formulation showed a comparative release profile similar to that the desired in-vitro target release profile, which followed zero order release kinetics and a stable formulation.Keywords: Controlled Release Formulation, Rivastigmine Tartarate, Anti-Alzheimer’s drug, HPMC K100M, Polyethylene oxide (PEO WSR303)

FABRICATION DEVELOPMENT, OPTIMIZATION AND CHARACTERIZATION OF GASTRORETENTIVE MICROSPHERES OF AN ANTIHYPERTENSIVE DRUG

The objective of the present study was to develop floating microspheres of Captopril in order to achieve an extended retention in the upper GIT which may enhance the absorption and improve the bioavailability. In the present study, preparation of captopril floating microspheres, evaluation of Floating Drug Delivery System (FDDS) in vitro, forecast of the release, and optimization of stirring speed and polymers ratio to match target release profile was investigated. The microspheres were prepared by solvent evaporation method using different ratio of hydroxyl propyl methyl cellulose (HPMC K4M) with drug in the mixture dichloromethane and ethanol at ratio of (1:1), with tween80 as the surfactant. Differential Scanning Calorimeter (DSC) study shows that drug and other excipients are compatible with each other. The effects of polymers concentration on drug release profile were investigated. The floating microspheres were characterized by and results obtained are % yield, particle size analysis, drug entrapment efficiency, surface topography, buoyancy percentage, in-vitro drug release was studied for 12 hour and scanning electron microscopy. Accelerated stability study was also performed for three months indicated that optimized formulation was stable. The floating microspheres showed better result and it may be use full for prolong the drug release in stomach and improve the bioavailability. The outcome showed that the polymer ratio and stirring speed affected the size, incorporation efficiency and drug release of microspheres (> 12 h), floating time (> 12 hr) and the best results were obtained at the ratio of HPMC K4M: EC (1:6). The mean particle size of prepared floating microspheres increased but the drug release rate from the microspheres decreased as the polymer concentration increased. The developed floating microspheres of captopril may be used for prolonged drug release for at least 12 hrs, thereby improving the bioavailability and patient compliance. Key words: Floating microspheres (FDDS), captopril, hydroxyl propyl methyl cellulose, ethyl cellulose, in-vitro release studies, bioavailability.