FORMULATION AND EVALUATION OF NEVIRAPINE MUCOADHESIVE MICROSPHERES

Objective: The objective of the present research was to formulate and evaluate HPMC K4M, HPMC K100, and Carbopol 940 Mucoadhesive microspheres in combination with sodium alginate for controlling release of Nevirapine. Methods: Nevirapine microspheres were prepared by an Ionotropic gelation method using aluminium sulfate as a cross linking agent. The developed Nevirapine microspheres were characterized for Micromeritic properties, morphology, drug entrapment efficiency, in vitro wash off test, in vitro drug release, and interaction studies (Fourier transfer infrared spectroscopy (FTIR) & Differential scanning calorimetry (DSC). Results: The Nevirapine mucoadhesive microspheres were free-flowing and discrete. The mean particle size ranged from 705.21±2.00 to 935.45±2.07 μm and the entrapment efficiencies ranged from 63.50 to 96.42 %. All the nevirapine microsphere batches showed good in vitro mucoadhesive property ranging from 03-68 % in the in-vitro mucoadhesive test after 8 h. FT-IR studies indicated the lack of nevirapine-polymer interactions in the nevirapine microspheres formulation. There were no compatibility issues and the crystallinity of nevirapine was found to be reduced in prepared mucoadhesive microspheres, which were confirmed by DSC and X-ray diffraction studies (XRD). Among different formulations, the nevirapine microspheres of batch F8 had shown the optimum percent drug entrapment and the controlled release of the nevirapine for about 12 h (98.65%). The Release pattern of nevirapine from microspheres of batch F8 followed the Korsmeyer- peppas and zero-order release kinetic model. The value of ‘n' was found to be 1.402, which indicates that the drug release was followed super case II transport type. Stability studies were carried out for F8 formulation at 4 °C/Ambient, 25±2 °C/60±5 %, 40±2 °C/75±5 % RH revealed that the drug entrapment and mucoadhesive behavior were within permissible limits. Conclusion: The results obtained in this present work demonstrate the potential use of HPMC K100 polymer for preparation of controlled delivery nevirapine mucoadhesive microspheres and prolonged residence at the absorption site.Â

BUCCAL PENETRATION ENHANCERS-AN OVERVIEW

Over the last decade, there has been a particular interest in delivering drugs in buccal mucosa and aiming to increase bioavailability of varied controlled drug delivery systems (CDDS), mucoadhesion (the capability of a object to adhere to mucous membranes) occupies a unique position. Buccal administration of API provides a convenient route of administration for both systemic and local actions. It provides direct entry into the systemic circulation thus avoiding the hepatic first-pass effect and degradation in the gastrointestinal tract. However permeability of oral mucosa is limiting factor which relatively low compared to intestinal mucosa and the skin. When permeability differences between various organs of the oral region are taken into consideration, buccal membrane found to be more permeable. In order to deliver wider classes of drugs across the buccal mucosa, the barrier potential of mucosa must be reduced. This requisite has forced the study of buccal penetration enhancers that will overcome the permeability barrier of the buccal mucosa. Numerous compounds have been evaluated for penetration enhancing activity, including bile salts, surfactants, fatty acids and derivatives, ethanol, cyclodextrins and chitosan etc. The purpose of this review is to identify the structural and chemical nature of the permeability barrier the buccal mucosa, to clarify the mechanisms of action of buccal penetration enhancers. &nbsp

PREPARATION AND EVALUATION OF MARAVIROC MUCOADHESIVE MICROSPHERES FOR GASTRO RETENTIVE DRUG DELIVERY

Objective: The objective of this research was to formulate and evaluate pectin and HPMC different grades mucoadhesive microspheres in combination with sodium alginate for controlled release of maraviroc.Methods: The maraviroc mucoadhesive microspheres was successfully developed by Ionotropic gelation technique, using sodium alginate, pectin, HPMC K4, K15, and K100 as mucoadhesive polymer in various proportions in combination. Further, the prepared maraviroc mucoadhesive microspheres were characterized for particle size, morphology, micrometric studies, entrapment efficiency, mucoadhesion, in vitro drug release, release kinetics, compatibility studies (FTIR) and stability studies.Results: The maraviroc Microspheres was discrete and free-flowing. The mean particle size ranged from 646.3±10.2 μm to 910.0±6.56 μm and the entrapment efficiency ranged from 50.80% to 91.43%. Entrapment efficiency of maraviroc microspheres was increased by increasing drug to mucoadhesive polymer ratio. Scanning electron microscopy revealed the rough surface morphology and no visible cracks of best formulation F16. The FTIR study confirmed the stable nature of maraviroc in the drug-loaded mucoadhesive microspheres. All the maraviroc microspheres showed good mucoadhesive property ranging from 04-73 % in the in-vitro wash off test after 8 hours. The Crystallinity of maraviroc was found to be reduced in prepared mucoadhesive microspheres, which were confirmed by XRD studies. The mechanism of maraviroc release from the mucoadhesive microsphere was found to be anomalous and super case-II transport type. Stability studies were carried out for the best formulation F16 indicates that there is no change in entrapment efficiency and percentage mucoadhesion of the formulation.Conclusion: The results obtained in this research work clearly indicated a promising potential of control release maraviroc mucoadhesive microspheres containing HPMC K100 as a rate controlling polymer for the effective treatment of AIDS/HIV patients.Â

FORMULATION AND IN VITRO EVALUATION OF LOSARTAN POTASSIUM MUCOADHESIVE BUCCAL TABLETS

Objective: The Losartan potassium mucoadhesive buccal tablet were prepared using mucoadhesive polymers such as Carbopol 940P, pectin, sodium CMC, Sodium alginate, HPMC K4M, HPMC K15M and HPMC K100M in alone and in combination as release retarding agent to prolong the drug release and to avoid first pass metabolism. Methods: The mucoadhesive buccal tablets were prepared by direct compression method. The prepared mucoadhesive buccal tablets were evaluated for physicochemical parameters such as hardness, thickness uniformity, weight variation, and surface pH and moisture absorption studies. The prepared buccal tablets were also evaluated for mucoadhesive strength, exâ€vivo residence time, in vitro drug release and drug permeation through porcine buccal mucosa. The drug excipients compatability was evaluated by DSC studies.   Results: Ex vivo mucoadhesive strength, ex†vivo residence time and in vitro release studies showed that formulation F10 containing 1:1.25 ratio of drug and polymer combination showed satisfactory bioadhesive and exhibited optimum drug release (91.33 % after 12hrs). DSC results showed no evidence of interaction between the Losartan potassium and mucoadhesive polymers. The results indicated that suitable bioadhesive buccal tablets with desired permeability could be prepared. The Stability of Losartan potassium mucoadhesive buccal tablets was determined in natural human saliva; it was found that both Losartan potassium and buccal tablets were stable in human saliva.   Conclusion: Hence different mucoadhesive polymers (Carbopol 940P, pectin, Sodium CMC, Sodium alginate and HPMC different grades) in various proportions can be used to prepare mucoadhesive buccal tablets of Losartan potassium having prolonged therapeutic effect with enhanced patience compliance by avoiding first pass metabolism.   Keywords: Losartan potassium, mucoadhesive buccal tablets, HPMC K100,Carbopol 940P,       Formulation, Evaluatio

FORMULATION AND EVALUATION OF LEVODOPA EFFERVESCENT FLOATING TABLETS

Objective: Levodopa is an immediate precursor of dopamine used in treatment of Parkinsonism disorders. The Levodopa effervescent floating tablets were prepared by direct compression technique, using different low density polymers (POLYOX different grades) in various drug polymer ratios.Methods: The Levodopa effervescent floating tablets were prepared by direct compression method. The floating tablets were evaluated for friability, thickness, hardness, weight variation test, drug content, in vitro release and floating properties. The drug excipients compatability was evaluated by DSC and FT-IR study.Results: All the batches showed compliance with pharmacopoeia standards. Among all the formulation F4 containing PEO WSR 303 in 1:1 drug polymer ratio showed controlled drug release for 12h (99.15%) emerging as the best formulation and follow first order kinetics via, swelling, diffusion. An in vitro buoyancy study reveals that all batches showed good in vitro buoyancy. The DSC study revealed that there was no strong interaction between Levodopa and excipients. Stability studies were carried out for best formulation F4 (PEO WSR 303 in 1:1 drug polymer ratio) according to ICH guidelines. Stability studies (40±2oC/75±5% RH) for 3 month indicated that Levodopa was stable in floating tablets.Conclusion: Hence different grades of low density polymer (PEO) in various drug polymer ratios can be used to prepare Levodopa floating tablets for prolongation of gastric residence time with enhanced patient compliance.Â

DEVELOPMENT AND EVALUATION OF RITONAVIR MUCOADHESIVE MICROSPHERES

  Objective: The objective of this research was to formulate and evaluate guar gum and ethyl cellulose mucoadhesive microspheres in combination with sodium alginate for controlled release of ritonavir.Materials and Methods: Microspheres were prepared by ionotropic gelation method using aluminum sulfate as a cross-linking agent. The developed ritonavir microspheres were characterized for micrometrics properties, morphology, drug entrapment efficiency, mucoadhesive property, in vitro drug release and interaction studies (Fourier transforms infrared spectroscopy [FTIR] and differential scanning calorimeter [DSC]).Results: The ritonavir mucoadhesive microspheres were free-flowing and discrete. The mean particle size ranged from 802.40±3.90 to 962.77±3.16 μm and the entrapment efficiencies ranged from 75.21 to 94.00%. All the ritonavir microsphere batches showed good in vitro mucoadhesive property ranging from 12 to 49% in the in-vitro wash off test. FTIR studies indicated the lack of ritonavir-polymer interactions in the ideal formulation F8. There were no compatibility issues and the crystallinity of ritonavir was found to be reduced in prepared mucoadhesive microspheres, which were confirmed by DSC and X-ray diffraction studies. Among different formulations, the ritonavir microspheres of batch F8 had shown the optimum percent drug entrapment of microspheres and the controlled release of the ritonavir for about 12 hrs. Release pattern of ritonavir from F8 microspheres batch followed Korsmeyers-Peppas and zero-order release kinetic model. The value of ‘n' was found to be 1.593, which indicates that the drug release was followed super Case-II transport type. Stability studies were carried out for F8 formulation at 4°C/ambient, 25±2°C/60±5%, 40±2°C/75±5% relative humidity revealed that the drug entrapment and mucoadhesive behavior were within permissible limits.Conclusion: The results obtained in this present work demonstrate the potential use of ethyl cellulose polymer for preparation of controlled delivery ritonavir mucoadhesive microspheres and prolonged residence at the absorption site.Keywords: Guar gum, Ethyl cellulose, Mucoadhesive microspheres, Ritonavi

DESIGN AND EVALUATION OF TORSEMIDE CONTROLLED RELEASE MATRIX TABLETS

 Objective: The controlled release Torsemide matrix tablets were prepared using different natural polymers in various proportions as releaseretarding agents to control the torsemide release and to improve the patient compliance.Methods: Torsemide matrix tablets were prepared by direct compression method. The matrix tablet is then evaluated for its thickness, hardness,friability, weight variation, drug content and in vitro release. The compatibility of drug excipients was reviewed using Fourier transform infrared (FTIR)and differential scanning calorimetry (DSC) studies.Results: All the torsemide matrix formulations showed compliance with pharmacopoeial standards. Amongst all the formulations, formulation F9containing pectin (10%) showed controlled drug release (99%) for 13 hrs, emerging as the best formulation. The formulation showed highest r2 valueof 0.9731 for zero order kinetics compared to first order kinetics indicating a drug release independent of concentration of the drug. Mechanism ofdrug release of optimized formulation F-9 showed non-Fickian diffusion. FTIR and DSC studies indicated no chemical interaction between the drugand polymer.Conclusion: Hence, different natural polymers (guar gum, xanthan gum and pectin) in various proportions can be used to prepare matrix tablets ofTorsemide having controlled therapeutic effect with improved patient compliance.Keywords: Torsemide, Guar gum, Xanthan gum, Pectin, Controlled Release, Matrix Tablets