In Silico Factorial Screening and Optimization of Chitosan Based Gel for Urapidil Loaded Microparticle using Reduced Factorial Design.

OBJECTIVE: Literature study revealed the poor mechanical strength of chitosan-based microparticles. Our research aimed at developing sufficient strength of microparticle with a suitable concentration of chitosan and non-ionic surfactants such as poloxamer-188 (pluronic). It also aimed to develop and study the effect of variables for prepared microparticles utilizing insilico screening methodology, such as reduced factorial design, followed by optimization. METHODS: Preliminary trial batches were prepared with variable concentration of chitosan and poloxamer-188 utilizing cross-linked ion-gelation technique. A 20% w/v sodium citrate solution was used as a cross-linking solution. The resolution-IV of 24-1 reduced factorial design was selected to screen the possible and significant independent variables or factors in the dosage form design. A total number of eight runs were suggested by statistical software and responses were recorded. The responses such as spreadability, pH, viscosity and percentage of drug released at 12 h were considered in the screening study. Based on the result, selected factors were included in the optimization technique, including graphical and numerical methods. RESULTS: The signified factors based on reduced two-level factorial screening design with randomized subtype, were identified by Half-normal and Pareto chart. Mathematical fitting and analysis were performed by the factorial equation during the optimization process. The validation and fitting of models were suggested and evaluated by p-value, adjusted R2, and predicted R2 values. The significant and non-significant terms were evaluated, followed by finding the optimal concentration and region with yellow color highlighted in an overlay plot. Based on the data obtained by the overlay study, the final formulation batch was prepared and the observed value was found to be pretty much nearer as compared to predicted values. Drug-polymer interaction study included attenuated total reflectance, differential scanning calorimetry, and X-Ray diffraction study. CONCLUSION: The principal of the study design was based on finding the prefixed set parameter values utilizing the concept of in-silico screening technique and optimization with a minimal number of trials and study expenses. It concluded that Poloxamer-188 (0.94%), chitosan (2.38%), swelling time (1.81 h), and parts of chitosan (78.51%) in a formulation batch would fulfill the predetermined parameter with specific values.

Chitosan Anchored Nanoparticles in Current Drug Development Utilizing Computer-Aided Pharmacokinetic Modeling: Case Studies for Target Specific Cancer Treatment and Future Prospective.

BACKGROUND: Recently, in the medical and pharmaceutical fields, biopolymers are extensively used for chemical and mechanical modifications of pharmaceutical dosage forms, which add novel properties, functions, and applications. Structural modification of dosage form by polymers along with redesigning in pharmaceutical and tissue engineering fields, presently being the center of analysis for the modern research world, which utilizes the subtle instruments, precise research strategies and most significantly the excipients. METHOD: The polymer, chitosan, which is a natural linear polysaccharide composed of randomly distributed ß-(1- 4)-linked D-Glucosamine and N-acetyl-D-Glucosamine units. Chitosan has been used by researchers as a network forming or gelling agent as chitosan is economically available, possesses low immunogenicity, biocompatibility, non-toxicity, biodegradability, protects against secretion from irritation and does not suffer the danger of transmission animal infective agent. Recent studies have proved that the chitosan conjugated in various biopharmaceutical drug formulations, such as nanoparticles, have been used for the treatment of breast, skin, colon, pancreatic, prostate and lung cancer. The nanoparticles have gained significant attention of scientific groups for relevant cancer-targeting drugs and dosage form. In this connection, several articles been published on chitosan anchored nanoparticles by suitable techniques, such as ion gelation, complexation, solvent evaporation, emulsion droplet coalescence and polymerization. RESULTS: The most remarkable point is that chitosan-drug conjugated nanoparticles (CDNP) can target cancer affected cells with the least attempt to killing the neighbor host cell. It is already proved that the CDNP facilitate the more drugs uptaking or cytotoxicity to a cancerous cell. This overcomes the dosage form designing problems of complexity in the biological mechanism and cell specificity. A computer-aided pharmacokinetic study as well as in-silico design with model fitting can provide the possible finding related to target selectivity and interaction. The computer aided study also reduces time and could make the entire process much cheaper till today, very few research has been reported, such as PyRx with AutoDock, response surface methodology and molecular dynamic simulation in drug delivery for chitosan-drug conjugated nanoparticles. CONCLUSION: Therefore, cancer cell target-specific drug delivery using a natural biopolymer conjugate with a computer-aided pharmacokinetic model will be the thirst area of future research. To get successful anticancer drug formulation, in-silico pharmacokinetic modeling would minimize labor, and expenses, during and prior to the experiment has been extensively discussed in the present review.

Formulation and evaluation of buccal patches for delivery of atenolol.

Buccal patches for the delivery of atenolol using sodium alginate with various hydrophilic polymers like carbopol 934 P, sodium carboxymethyl cellulose, and hydroxypropyl methylcellulose in various proportions and combinations were fabricated by solvent casting technique. Various physicomechanical parameters like weight variation, thickness, folding endurance, drug content, moisture content, moisture absorption, and various ex vivo mucoadhesion parameters like mucoadhesive strength, force of adhesion, and bond strength were evaluated. An in vitro drug release study was designed, and it was carried out using commercial semipermeable membrane. All these fabricated patches were sustained for 24 h and obeyed first-order release kinetics. Ex vivo drug permeation study was also performed using porcine buccal mucosa, and various drug permeation parameters like flux and lag time were determined.