DEVELOPMENT OF ROPINIROLE (FREE BASE) TRANSDERMAL PATCH US ING BLENDS OF HYDROXYPROPYL METHYLCELLULOSE/EUDRAGITS AND IT’ S IN VITRO/ IN VIVO CHARACTERIZATION

The objective of this study was toprepare and evaluate a matrix type transdermal patch ofropinirole using blends ofhydroxypropylmethylcellulose (HPMC) and EudragitRL 100 and HPMC and Eudragit ERS100. Materialsand Methods: Ropinirole free based used as the drugentity was prepared from its hydrochloride salt.Suitability of the polymers in the form of drug-excipientcompatability was determined prior to formulationdevelopment using FTIR. Patches were developed usingsolvent evaporation technique. Limonene was used asa penetration enhancer. Moisture absorption,moisture content and mechanical properties, drugcontent, in vitro drug release, drug-excipient compatibility,in vitro skin permeation were the in vitro parametersmeasured. Short-term stability, skin irritation andin vivo drug release were measured with oneoptimized formulation. Results and discussion:Ropinirole free base was used successfully in thepreparation of the patches. FTIR studies indicated nointeraction between the drug and the polymers of thisstudy. Formulations developed were strong and notbrittle with uniform drug release. Patches containinghigher HPMC generally showed higher drug releaseand permeation. Drug release and permeation decreasedwith increase in the concentrations of Eudragits. Drugrelease studies indicated Higuchi model for all thepatches with a diffusion mechanism of non-fickian type.Short-term stability studies indicated that ropinirolewas stable in the patches. Patches did not cause any skinirritation. In vivo the optimized patch sustained drugrelease for 24 hours upon one time administration.Conclusion: Clinically viable ropinirole transdermalpatch can be successfully prepared from its base formusing HPMC/Eudragits

ENHANCED LIVER DELIVERY AND SUSTAINED RELEASE OF CURCUMIN WITH DRUG LOADED NANOPARTICLES AFTER INTRAVENOUS ADMINISTRATION IN RATS

Liver targeting drug delivery systems can improve thedelivery of several drugs useful in the treatment of liverdisorders such as cirrhosis and liver cancer. Theobjective of this study was to prepare the biodegradablenanoparticles containing curcumin, a well-knownhepatoprotective agent and further to evaluate the livertargetability and sustained release of curcumin with thedeveloped nanoformulation. Curcumin nanoparticleswere prepared by double emulsion (w/o/w) solventevaporation method using different drug polymer ratios.Poly-ε-caprolactone was used in the preparation. Theprepared formulations were evaluated for particles size,surface potential, entrapment efficiency, in vitro release,drug polymer interaction. Four different formulationsCNP1, CNP2, CNP3 and CNP4 were prepared.Optimized formulation (CNP3) was evaluated forpharmacokinetics and hepatoprotective activity in CCl4induced liver toxicity model after i.v. administration.Optimized formulation was selected based on the size,entrapment efficiency and release characteristics.Curcumin i.v. solution and oral suspension form wereused as the reference. Particle size of all formulationswas in the range of 300-470 nm and the entrapmentefficiencies were in the range of 75-85 %. Drug releasefrom the nanoparticles was sustained both in vitro and invivo. Nanoparticle formulation tested in vivodemonstrated better pharmacokinetics andpharmacodynamics compared to the reference. Druglevels in the liver were significantly higher withnanoparticular formulation. Thus, this studysuccessfully prepared a nanoparticular formulationcontaining curcumin with polycaprolactone as thepolymer. With the developed formulation better livertargetability was achieved

Preparation and in vitro/in vivo characterization of curcumin microspheres intended to treat colon cancer

Objective: The objective of the present investigation was to prepare colon targeted curcumin microspheres using Eudragit S100 and evaluate the same for in vitro/in vivo properties. Materials and Methods: A "O/O solvent evaporation" technique was used in the preparation of microspheres. The influence of various process variables including stirring speed, drug:polymer ratio and percentage of emulsifier on the fabrication were investigated and the formulation was optimized. Prepared microspheres were evaluated for in vitro and in vivo properties. Surface morphology, particle size, percentage drug entrapment, percentage yield, drug polymer interaction, in vitro drug release in simulated gastrointestinal transit conditions and stability were the in vitro parameters investigated. Using an optimized formulation, drug release into the systemic circulation and organ distribution were investigated as in vivo parameters. In vivo parameters were estimated in male albino rats. Results: Curcumin microspheres of Eudragit S100 were successfully prepared using o/o solvent evaporation method. Microspheres prepared using 1:2 drug:polymer ratio, with a stirring speed of 1000 rpm, and using 1.0% w/v concentration of emulsifying agent was selected as an optimized formulation. The release studies with optimized formulation demonstrated that aqueous solubility of curcumin was enhanced by 8 times with the formulation. FTIR studies demonstrated no change in drug characteristics upon microsphere fabrication. The enhancement in solubility is thus due to the increase in the surface area of the drug substance and not due to a change of drug to a different physical state. This was further confirmed by scanning electron microsphere pictures. Drug release followed Korsmeyer and Peppas release model. Accelerated stability studies indicated that the drug is stable in the formulation for a period of atleast 14 weeks at room temperature. In vivo studies demonstrated a sustained drug release into the systemic circulation after oral administration of the formulation. Further, colon target was affectively achieved using the optimized formulation. Eudragit microspheres delivered most of their drug load (79.0%) to the colon, whereas with plain drug suspension only 28.0% of the total dose reached the target site. Conclusion: This study successfully developed curcumin microspheres that can be used effectively in the treatment of the colon cancer

Development and Evaluation of a Chloramphenicol Hypertonic Ophthalmic Solution

Hypertonic ophthalmic solutions are used to treat ocular diseases associated with edema. In this study, we developed a chloramphenicol hypertonic ophthalmic solution. These drops were developed based on the cosolvency and additional dielectric constant concepts. Two different solvents: PEG 300 and glycerol were used as cosolvents. Solubility curves were plotted. Based on the solubility curves, two different solutions were selected. These solutions were evaluated for physical parameters and accelerated stability. The results indicated that chloramphenicol was stable in these formulations. The selected blend of solutions was hypertonic. Thus, the solubility and stability of chloramphenicol was enhanced using a cosolvency technique so as to develop a chloramphenicol hypertonic ophthalmic solution

Pulmonary Delivery of Voriconazole Loaded Nanoparticles Providing a Prolonged Drug Level in Lungs: A Promise for Treating Fungal Infection

Current therapies are insufficient to prevent recurrent fungal infection especially in the lower part of the lung. A careful and systematic understanding of the properties of nanoparticles plays a significant role in the design,development, optimization, and in vivo performances of the nanoparticles. In the present study, PLGA nanoparticles containing the antifungal drug voriconazole was prepared and two best formulations were selected for further characterization and in vivo studies. The nanoparticles and the free drug were radiolabeled with technetium-99m with 90% labelling efficiency, and the radiolabeled particles were administered to investigate the effect on their blood clearance, biodistribution, and in vivo gamma imaging. In vivo deposition of the drug in the lobes of the lung was studied by LC−MS/MS study. The particles were found to be spherical and had an average hydrodynamic diameter of 300 nm with a smooth surface. The radiolabeled particles and the free drug were found to accumulate in various major organs. Drug accumulation was more pronounced in the lung in the case of administration of the nanoparticles than that of the free drug. The free drug was found to be excreted more rapidly than the nanoparticle containing drug following the inhalation route as assessed by gamma scintigraphy study. Thus, the study reveals that pulmonary administration of nanoparticles containing voriconazole could be a better therapeutic choice even as compared to the iv route of administration of the free drug and/or the drug loaded nanoparticles