DEVELOPMENT OF NANOPARTICLES SUSPENSION FOR PAEDIATRIC DRUG ADMINISTRATION

Objective: Enalapril maleate (EM) is an angiotensin-converting enzyme (ACE) inhibitor. It is generally prescribed for the treatment of hypertension, heart failure and chronic kidney diseases in adults and children. EM 2.5 mg, 5 mg, 10 mg and 20 mg tablets and EM injection 1.25 mg/ml are currently available in the market. But a liquid paediatric formulation of this medicine is not currently available. Also, it is a BCS class III drug, having a bioavailability of approximately 60%. The present study proposes a new strategy for improvement of drug bioavailability and taste masking: EM nanoencapsulation within polymeric nanoparticles suspensions prepared with Eudragit RS100 (ERS100) as polymer and Tween 80 as a stabilizer, aiming at obtaining a liquid dosage form suitable for paediatric administration.Methods: Nanoprecipitation method used for the preparation of nanoparticles suspension. The preparations were evaluated for drug content, entrapment efficiency, particle size, zeta potential, polydispersity index, pH, viscosity and in vitro drug release. Based on the entrapment efficiency, viscosity and in vitro drug release the optimized formulation was selected. Optimized formulation evaluated for taste, ex vivo intestinal permeation, differential scanning calorimetry, scanning electron microscopy and release kinetic studies.Results: The optimized nanoparticle formulation F8 having drug to polymer ratio of 1:100 showed satisfactory drug content (95.1%), entrapment efficiency (77.71%), particle size (198.47 nm), pH (6.36), viscosity (2.9 x〖10〗^(-3)Pa•s) and 81.2% drug release after 12 h. The formulation has taste-masking properties and shows 84.6% drug permeation through the goat intestine within 12 h.Conclusion: The prepared nanoparticles suspension of Enalapril maleate was found to be an effective liquid pharmaceutical dosage form for paediatric administration with taste-masking properties

DEVELOPMENT AND CHARACTERIZATION OF TACROLIMUS TABLET FORMULATIONS FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to prepare and characterize inclusion complexes of tacrolimus with β-cyclodextrin to improve its solubility and to formulate them into sublingual fast disintegrating tablets with a view to bypass the first-pass metabolism. Methods: Tacrolimus: β-cyclodextrin inclusion complexes (1:1 and 1:2 molar proportions) were prepared using the kneading method. Their characterization was accomplished by determining the drug content, solubility, Attenuated Total Reflection-Infrared Spectroscopy (ATR-IR), Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and powder X-Ray Diffraction analysis (pXRD). These were then formulated to fast disintegrating tablets and evaluated for precompression as well as post compressional characteristics. Results: SEM analysis showed the inclusion complexes as rough, non-porous, irregular surfaced aggregate particles. DSC and pXRD analyses confirm the crystallinity change and partial conversion to the amorphous form of the drug in the inclusion complexes. From the solubility studies, it was observed that both the inclusion complexes of 1:2 molar ratio (14.82±0.889 µg/ml) and 1:1 molar ratio (12.72±0.1004 µg/ml) improved the aqueous solubility to greater extents in comparison to that of the pure drug (3.05±0.121 µg/ml). All the tablet formulations showed good precompression and mechanical properties. The inclusion complex loaded tablets exhibited a superior drug release pattern when compared to tablets prepared with tacrolimus alone. The optimized formulation (TT3) showed an in vitro disintegration time of 34.33 s and a percent drug release of 97.87. Conclusion: The inclusion complex formulation combined with the sublingual route of administration can be expected to result in an improved bioavailability of tacrolimus by increasing its solubility and bypassing first-pass metabolism

DEVELOPMENT OF NANO BASED FILM FORMING GEL FOR PROLONGED DERMAL DELIVERY OF LULICONAZOLE

Objective: Luliconazole (LZL) has low aqueous solubility that limits its dermal bioavailability and acts as a barrier to topical delivery. The conventional topical formulations have a limited ability to retain the drug over the skin for a prolonged period. The main objective of the study was to formulate and characterize LZL loaded ethyl cellulose (EC) nanoparticles and formulate them as a film-forming gel (FFG) for prolonged delivery in fungal skin infections.Methods: The solvent evaporation technique was used for the preparation of nanoparticles of LZL by using EC as a polymer. The prepared nanoparticles were evaluated for physical appearance, production yield, entrapment efficiency, drug content, particle size, zeta potential, Polydispersity index (PDI), and in vitro drug release. Then the nanoparticles were incorporated into FFG formulation by using polyvinyl pyrrolidone (PVP) and polyvinyl alcohol (PVA) as the gelling agent. The prepared FFG was evaluated for pH, Viscosity, Spreadability, in vitro drug release studies, in vitro antifungal studies, and release kinetic studies.Results: The optimized nanoparticle formulation F5 having drug to polymer ratio of 1:2 showed satisfactory production yield (86.32%), entrapment efficiency (83.36%), drug content (42.86), particle size (125.3), and 93.72% of in vitro drug release after 24 hours (h). The optimized FFG formulation FFG4 showed the shortest film-forming time of 5.06 minutes (min), percentage Cumulative drug release of 92.18% after 24 h, and had promising in vitro antifungal activity.Conclusion: The prepared FFG could be used with promising potential for fungal infection of the skin

IMPLEMENTING CENTRAL COMPOSITE DESIGN FOR THE DEVELOPMENT OF TACROLIMUS FILM FOR SUBLINGUAL ADMINISTRATION

Objective: The study aimed to develop fast-dissolving films (FDFs) of the immunosuppressant drug tacrolimus monohydrate for sublingual administration, employing central composite design (CCD) to improve its bioavailability. Methods: Tacrolimus: β- cyclodextrin inclusion complexes prepared earlier were transformed into FDFs. CCD was used for attaining optimal film formulation with the desired characteristics. The solvent casting method was used for the preparation of films. For optimization, the independent variables selected were the concentration of hydroxy propyl methyl cellulose E5 (HPMC E5) (X1) and concentration of croscarmellose sodium (CCS) (X2) and the responses were disintegration time (Y1) and percentage drug release at 5 minutes (Y2). The suggested optimal films were subjected to further characterization. Results: All the formulations showed good mechanical properties. The composition of optimized FDFconstituted3.016% w/v of HPMC and 11.731%w/wofCCSand its average disintegration time was27.28s and showed 83.13 % mean drug release at 5 minutes. Differential Scanning Calorimetry (DSC) analysis showed complete dispersion and partial conversion into the amorphous form of the drug which was also confirmed by X-ray diffraction (XRD) studies. Scanning Electron Microscopy (SEM) revealed the smooth and porous nature of the film. Conclusion: The developed FDF may be used sublingually for delivering tacrolimus efficiently, avoiding its oral bioavailability problems