FORMULATION DEVELOPMENT OF SUSTAINED RELEASE INTRA-ARTICULAR INJECTION OF ANALGESIC DRUG

The purpose of this study was to formulate and evaluate Parenteral Intraarticular Sustained-Release Formulation of an analgesic drug using the technology of in situ forming gel, based on temperature change mechanism in order to reduce the frequency of dosing and increase patient compliance in the treatment of knee pain. The formulation was optimized, prepared, filled aseptically, sterilized and evaluated for prerequisites of parenteral and other parameters like gelation temperature, gel strength, viscosity, drug content, in vitro and in vivo studies and stability studies. It was prepared using cold method and optimized by 32 factorial design, comprising of drug, Pluronic F127, HPMC K 100M and HPMC K4M was found to be clear, colorless, isotonic, sterile, pH as 6.8-7, viscosity of 1800 cps, syringeable through 18 gauze needle, forming a stable in-situ gel at knee joint temperature having gel strength of 43.80 gm/cm showing a drug release of 95.88 % in phosphate buffer pH 7.4 at 120hrs. The sterile formulation packed in transparent ampoule was found to the stable with most suitable storage condition at the refrigerator temperature. Thus a biocompatible, stable parenteral formulation was developed which can be an alternative and convenient approach to the patients that require frequent parenteral administration, reducing the frequency of dosing and ultimately increasing patient compliance and comfort. Keywords: Tramadol HCL, In situ gel, Pluronic F127, intra-articula

DEMONSTRATION OF LYMPHATIC UPTAKE OF (6)-GINGEROL SOLID LIPID NANOPARTICLES

(6)-Gingerol, a disease modifying anti-rheumatoid drug (DMARD) agent in the treatment of Rheumatoid Arthritis is a potent inhibitor of COX-1, COX-2 activity, inhibits PGE2 production. It also inhibits the production of TNF-α by blocking the cell associated conversion of TNF precursor to mature proteins thus, halting the proliferation of synovitis. (6)-Gingerol undergo extensive phase I metabolism & underlies low systemic exposure. The aim of the present study was to overcome these limitations and formulate and evaluate Ginger extract Solid Lipid Nanoparticles to improve bioavailability by enabling lymphatic uptake. (6)-Gingerol Solid Lipid Nanoparticles were prepared by melt emulsification-homogenization method and the particle size, Zeta potential PDI and % entrapment efficiency was optimized using Box Behnken design. The optimized SLN were found to be 237nm in size, bearing -25.3mv zeta potential, 0.350 PDI and entrapment efficiency of 91.33%.  Ex vivo endocytic uptake studies (everted intestine method) revealed involvement of endocytic pathways in the uptake of Solid Lipid Nanoparticles from intestine. Thus underlining the utility of SLN for enhancement of uptake of (6)-Gingerol

Nanoparticulates of Fenofibrate for Solubility Enhancement: Ex-Vivo Evaluation

The aim of present research work was to formulate and evaluate nanosuspension of fenofibrate which is categorized as BCS class II agent. With an intention to increase solubility and dissolution rate of fenofibrate nanosuspension were prepared by high pressure homogenization method, a top down technique. Using poloxamer 188 and Tween 80 as a stabilizer. Formulation scheme was developed by Box Behnken Design. Formulation factor which affect the particle size includes Concentration of surfactant and processing parameters includes Homogenization pressure and Homogenization cycles. In this study practically water insoluble fenofibrate was nanosized and surfactant was added for their stabilizing effect. In vitro dissolution study showed that the increase in the release rate of fenofibrate from nanoparticles as compared to pure drug. Scanning electron microscopy study showed that the spherical morphology of nanoparticles. Particle size distribution, zeta potential, crystal form of formulated nanosuspension were studied by using particle size analyzer, and X-ray powder diffraction, Ex-vivo study for calculating absorption rate. The result showed that the drug dissolution rate in nanosuspension formulation is depends upon the crystal form, solubility, procedure involved, and stabilizer used. Keywords: Solubility, Dissolution, high pressure homogenization, lyophilization, nanosuspension

FORMULATION OF AN INSITU FORMING INJECTABLE SUSTAINED RELEASE SPONGE OF GRANISETRON HYDROCHLORIDE

The overall aim of this work was to develop sustained release parenteral drug delivery system involving formation of an insitu sponge of an anti-emetic drug typically co-administered inchemotherapy induced nausea and vomiting. The study involved formulation of the drug Granisetron Hydrochloride in a sponge forming gelatin matrix as a dry powder for reconstitution into a suspension to be injected into the body forming a sponge insitu intended to release the drug over a period of 5 days. The formulation was prepared by the method cryogelation and optimised using gelatin5% as a sponge forming polymer, crosslinking agent glutaraldehyde 0.3% , sustained release retardant Hydroxypropylmethyl cellulose K100M 1% (HPMC K100M) and suspending agent sodium carboxymethylcellulose 1% (NaCMC) to form a  solution intended to be administered subcutaneously.The formulation was evaluated for all prerequisites of parenteral and other parameters of gelatin matrix like swelling index, surface scanning microscopy .for injectable suspension, sedimentation study, particle size,zeta measurement, invitro drug release, and stability studies. The formulation was found tosterile, isotonic, having swelling index 88% and SEM 100-120 μm,particle size 0.765μm.with zeta potential-14.2 mV, swelling time was 10 min. The in vitro drug release was found to be over 93.20% in Simulated Body fluid pH 7.4 at 37°C over a prolong period of 5days The formulation was physically and chemically stable at accelerated conditions for period of 1 month

FORMULATION DEVELOPMENT OF SUSTAINED RELEASE EPIDURAL INJECTION OF ANALGESIC DRUG

The objective of this work was to formulate and evaluate sustained release epidural injection of analgesic drug diclofenac sodium used in chronic lower back pain. The formulation composed of a thermosensitive polymer Pluronic F127 (20%) and sustained release copolymers HPMC K100M (1%) and HPMC K4M (0.5%) optimized using 32 factorial design. The formulation was found to be clear, colorless, sterile, syringeable through 18gauge, forming a stable gel at 37°C with a gel strength of 9.67g/cm. The drug release was found to be 98.13% in 72 hrs. The formulation was found to be stable at refrigerator temperature of 5°C for a month. Thus, a stable parenteral formulation was developed that can be an appropriate and convenient approach for patients requiring frequent parenteral administration, reducing recurrence of dosage and ultimately expanding patient comfort and satisfaction in case of chronic ailments

Preformulation Studies of Intranasal Solid Lipid Nanoparticles of Mometasone Furoate

The objective of the present work was to prepare intranasal solid lipid nanoparticles (SLN) of mometasone furoate. Mometasone furoate is BCS class II drug having low aqueous solubility and highly sensitive to hepatic metabolism. Mometasone furoate loaded nanoparticles were prepared by high pressure homogenization technique. The preformulation studied was conducted by studying various selection criteria. Lipid was chosen on the basis of maximum solubility of the drug in lipid. Glyceryl monostearate was selected as the lipid phase which showed maximum drug solubility than other lipids. Selection of surfactant, homogenization pressure and no. of homogenization cycle was done on the basis of minimum particle size and maximum % entrapment efficiency. These results showed high entrapment efficiency and minimum particle size. Keywords: Intranasal solid lipid nanoparticles, High pressure homogenization, Glyceryl monostearate

Taste masking of cefuroxime axetil by ion exchange resin complex

The antibiotic cefuroxime axetil is extremely bitter. The present study deals with development of taste-masked resinates of cefuroxime axetil using ion exchange resins. The drug resin complexation procedure was optimized with respect to drug to resin ratio and pH of medium. Taste masked complex was characterized by FTIR, DSC and XRPD studies. In vitro release studies revealed complete drug release from the complex within 120 min in 0.1N HCl solution whereas less than 5 % drug was released from taste masked complex in 60 sec in simulated salivary fluid (pH 6.2) which found to be insufficient to impart bitter taste. The taste-masked complex was then formulated into a suspension dosage form using sodium carboxymethyl cellulose as suspending agent. The suspension was evaluated for various quality control parameters and in vivo studies were carried out to check bioavailability of drug from suspension.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Formulation and in-vitro evaluation of repaglinide microspheres prepared by spray drying technique

Repaglinide is a potent second generation oral hypoglycaemic agent widely used in treatment of non insulin dependent diabetic mellitus. The objective of the present study was to develop sustained release microspheres of repaglinide using ethyl cellulose and PEG 6000 as a matrix forming polymer. Microspheres were prepared by taking various concentrations of ethyl cellulose and PEG 6000 by spray drying technique. Prepared microspheres were evaluated for process yield, drug entrapment, particle size, SEM, FTIR, DSC and in vitro drug release. Process yield and drug entrapment was 40-45 % and 90-95 %, respectively. Particle size ranged in 5-22 µm and SEM study showed spherical shape and rough surface of microspheres. FTIR study and DSC analysis revealed the stable nature and amorphous dispersion of drug in the polymer matrix. In vitro release studies indicate retardation of release upto 12 h which can control both fasting blood glucose level and postprandial blood glucose.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Development of Hot Melt Coating Technique for Taste Masking of Chloroquine Phosphate Tablets

In the present study to mask the unpleasant taste of chloroquine phosphate, hot melt coating technique was used as a taste masking tool. Hot melt coating is a solvent free technology grants rapid, additionally economical coating process with reduced risk of dissolving drug during process and provide uniform application rate of coating agent. Precirol ATO 5 was used as hot melt coating material for taste masking. Tablets were prepared by wet granulation method and coated using hot melt coating technique. Coated tablets exhibited good uniformity of drug content. Amount of drug release from all batches were evaluated. Taste evaluation of hot melt coated tablets was done by using electronic tongue.PrecirolATO5 was found to be a better taste masking agent when used by hot melt coating technique. Keywords: Precirol ATO 5, Hot melt coating, taste masking

Dissolution Improvement of Poorly Water Soluble Drug Valsartan and Improving Flow Properties of Solid Dispersion

The aim of the present investigation is to improve the dissolution of poorly water soluble drug valsartan by preparing solid dispersions and also to evaluate the effect of different inert carriers on flow properties of solid dispersion. Valsartan is a poorly soluble drug useful in the treatment of hypertension. Absorption window of valsartan is stomach and upper part of small intestine. One possible way to improve dissolution rate is solid dispersions of the drug. The solid dispersions were prepared by solvent evaporation method using HPMC E5 LV as water soluble carrier, as use of HPMC low viscosity polymers for solid dispersion preparations were reported in literature. But film formation took place during solid dispersion formulation and was creating difficulty in releasing the drug from formulation; and those solid dispersions, were not free flowing. Thus such preparations are not useful from the formulation development point of view. So to improve the flow properties some inert material were tried like microcrystalline cellulose (MCC) and lactose. The solid dispersions were evaluated for drug content, solubility and dissolution studies. In vitro drug release of solid dispersions was studied by USP type II paddle dissolution apparatus. For the solid dispersion the solubility and dissolution of the drug increased with the increase in the carrier concentration. Probable mechanisms of improved solubility and dissolution were characterized by Differential Scanning Calorimetry (DSC), Powder X-ray Diffractometry (Powder XRD) and Scanning Electron Microscopy (SEM) of drug, physical mixture and solid dispersions. This study revealed that solid dispersions technique is promising and useful for valsartan to improve its solubility and dissolution and incorporation of inert carriers improved the flow property of solid dispersion.Colegio de Farmacéuticos de la Provincia de Buenos Aire