Formulation Consideration and Skin Retention-Permeation Study of Insitu Nanogel Containing Dimethylfumarate for Treatment of Psoriasis

Aims and Objective: to develop and evaluate an insitu nanogel formulation containing dimethylfumarate for targeted topical delivery therapy of psoriasis. Study Design: 32 full factorial design Place and Duration of Study: Department of Pharmaceutics, Parul Institute of Pharmacy and Research, Parul University, Vadodara, between 2016 to 2019. Methodology: Nanogel were formulated by chemical cross linked gel method using Polyvinyl alcohol and Hyaluronic acid (1:5) ratio using Glutaraldehyde (GA) (25 %w/v) and Hydrochloric acid (HCl) (6%v/v) as a crosslinking agent and catalyst. Dimethylfumarate loaded nanogel were clear and showed physicochemical parameters desired for topical delivery and stability. Results: The Permeation profile of dimethylfumarate through rat skin from selected nanogel formulation exhibited highest skin uptake. The Micoscopic observations indicated that the optimized nanogel had n significant effect on the microscopic structure of the sin and epithelial cells appered mostly unchanged. The surface epithelium lining and the granular cellular structure of the skin were totally intact. The developed Nanogel may be a potential drug delivery vehicle for targeted topical delivery of dimethylfumarate in the treatment of psoriasis. Conclusion: As per drug retention study the highest amount of drug retained on the skin and lowest amount of drug permeate to the skin. Hence it was observed that there was no significant correlation between skin retention and skin permeation study.

Formulation and Evaluation of Miconazole Nitrate Loaded Novel Nanoparticle Gel for Topical Delivery

The aim of the present research work is to design miconazole-loaded chitosan nanoparticles that could potentially assemble in wrinkle and hair follicles to provide prolong release to the skin tissue. The amount of drugs required for the preparation of nanoparticles was determined by studying the entrapment efficiency of preliminary batches. The emulsification/Solvent evaporation method was used for the preparation of nanoparticles. Different proportions of Miconazole Nitrate and Chitosan were dissolved in DCM. The size of the globules in the emulsion was reduced by a high energy shearing using a probe Sonicator at 50 % amplitude for 10 Minutes, followed by the addition of 10 ml 2% PVA. After overnight evaporation of DCM, for isolation of dried NPs, the NPs dispersion was centrifuged at 15,000 RCF for 30 minutes. The obtained particles were dispersed in de-ionized water and freeze-dried. 32 full factorial design was selected for optimization purposes. Prepared batches were evaluated for various parameters such as entrapment efficiency, production yield, particle size, zeta potential, and SEM. F5 batch was found to be optimized which was then used for the preparation of gel. Three levels of Carbopol934 and propylene glycol were used for the optimization of gel. The prepared gel was also evaluated for pH, drug content, viscosity, and spreadability. From the study, it was concluded that nanoparticle gel can be used for the treatment of various skin infections over the conventional gel.

FORMULATION OPTIMIZATION AND EVALUATION OF TINIDAZOLE IN-SITU

The study deals with formulation optimization and evaluation of tinidazole gel by using sodium alginate as gelling agent calcium chloride, sodium citrate were used as cross linking agent. The polymeric solution of drug is in solution form before it administered to the body. But after administration when it comes in contact with acidic pH it’s converted into gel form and the drug tinidazole released from the dosage form constantly and slowly. The formulation is effective for the treatment of gastric ulcer because of Helicobacter pylori. 32 full factorial design were used for the optimization of the formulation 12 trial batches were prepared and 9 factorial design batches in which 2 factor 3 level factorial design were used for the optimization. The concentration of sodium alginate, were taken in 3 level low, medium, high and the prepared formulation were evaluated.

FORMULATION, OPTIMIZATIONANDEVALUATION OF SUBLINGUAL FILM OF ENALAPRILMALEATE USING 32 FULL FACTORIAL DESIGN

Objective: The purpose of this investigation was to formulate, optimize and evaluate sublingual film of Enalapril maleate for rapid management of Hypertension. Methods: Sublingual films were prepared by solvent casting method. Present investigation were formulated by using HPMC E 15 (X1) as polymer and Polyethylene glycol (X2) as plasticizer were chosen as independent variables in 32 full factorial design while Tensile strength (TS), Disintegration time (DT) and % Cumulative drug release at 10 min. (% CDR) were taken as dependent variables. The various physical parameters were evaluated for sublingual films such as thickness, tensile strength, folding endurance, disintegration time, surface pH and % CDR. Results: From the experimental study, it was concluded that the optimized batch F8 showed 98.6 %, the highest release of the drug. Stability study was performed by taking an optimized formulation and it was observed stable. The sublingual films showed acceptable results in all studies such as thickness, tensile strength, folding endurance, disintegration time, surface pH and % CDR at 10 min. R2 values for Tensile Strength (Y1), Disintegration time (Y2) and % cumulative drug release at 10 min. of Enalaprilmaleate(Y3) found to be 0.9852, 0.9829 and 0.9641 respectively. Thus, a good correlation between dependent and independent variables was developed. Conclusion: 32 full factorial design was successfully applied during preparation, optimization and evaluation of sublingual films of Enalapril maleate. The present investigation showed quick disintegration and fast release of the drug for rapid management of Hypertension.

Development and Optimization of Inhalable Levofloxacin Nanoparticles for The Treatment of Tuberculosis.

Background:: Levofloxacin has been recommended by WHO for the treatment of pulmonary tuberculosis and inhalable delivery of levofloxacin can be advantageous over conventional delivery. Objective:: This study aimed to develop and optimize inhalable levofloxacin loaded chitosan nanoparticles (LCN). The objective was to achieve the mean particle size of LCN less than 300nm, sustain the drug release up to 24 h and achieve MMAD of LCN of less than 5μm. Methods:: LCN were prepared by ionic gelation of chitosan with sodium tripolyphosphate (STPP) and subsequent lyophilization. A Plackett Burman screening design, 32 full factorial design, and overlay plot were sequentially employed to optimize the formulation. The mean particle size, % entrapment efficiency, in vitro drug release, and Minimum inhibitory concentration were evaluated. Results:: The Pareto chart from Placket Burman screening design revealed that the concentration of chitosan and concentration of STPP were found to be significant (p < 0.05). Further analysis by 32 full factorial design revealed that F-ratio for each model generated was found to be greater than the theoretical value (p < 0.05), confirming the significance of each model. Conclusion:: The optimized formulation showed a mean particle size of 171.5 nm, sustained the drug release up to 24 h in simulated lung fluid, and revealed MMAD of 3.18 μm, which can confirm delivery of the drug to deep lung region. However, further in vivo studies are required to design suitable dosage regimen and establish the fate of nanoparticles for safe and efficacious delivery of the drug.

Application of 32 Full Factorial Design and Desirability Function for Optimizing The Manufacturing Process for Directly Compressible Multi-Functional Co-Processed Excipient

Background: Developing a new excipient and obtaining its market approval is an expensive, time-consuming and complex process. Compared to that, the co-processing of already approved excipients has emerged as a more attractive option for bringing better characteristic excipients to the market. The application of the Design of Experiments (DoE) approach for developing co-processed excipient can make the entire process cost-effective and rapid. Objective: The aim of the present investigation was to demonstrate the applicability of the DoE approach, especially 32 full factorial design, to develop a multi-functional co-processed excipient for the direct compression of model drug - cefixime trihydrate using spray drying technique. Methods: The preliminary studies proved the significant effect of atomization pressure (X1) and polymer ratio (microcrystalline cellulose: mannitol - X2) on critical product characteristics, so they were selected as independent variables. The angle of repose, Carr’s index, Hausner’s ratio, tensile strength and Kuno’s constant were selected as response variables. Result: The statistical analysis proved a significant effect of both independent variables on all response variables with a significant p-value < 0.05. The desirability function available in Design Expert 11® software was used to prepare and select the optimized batch. The prepared co-processed excipient had better compressibility than individual excipients and their physical mixture and was able to accommodate more than 40 percent drug without compromising the flow property and compressibility. Conclusion: The present investigation successfully proved the applicability of 32 full factorial design as an effective tool for optimizing the spray drying process to prepare a multi-functional co-processed excipient.