Factorial design

The purpose of this study was to develop chitosan based anastrozole nanoparticles for treatment of breast cancer. An ionic gelation method was used to prepare anastrozole controlled-release nanoparticles. A 32 full factorial design was employed. Experimental variables such as concentration of CS and cross-linking agent sodium TPP were varied to study their effect on drug entrapment efficiency and release rates of drug from nanoparticles. Fourier transform infrared spectroscopic (FTIR) analysis and differential scanning calorimetry (DSC) were employed to determine any interactions between drug and polymer. The FTIR studies revealed no chemical interaction between the drug and the polymer. Entrapment efficiency of nanoparticles ranged between 51.51 ± 0.81 % to 84.35 ± 1.06 %.In-vitro release studies were performed in phosphate buffer saline of pH 7.4. A slow release of anastrozole up to 72 h was observed. Mean particle size of nanoparticles ranged between 1635 nm to 72.30 nm with mean particle size of 273.6 nm, while zeta potential 0.52 mV. DSC results indicated that the anastrozole entrapped in the nanoparticles existed in an amorphous or disordered-crystalline status in the polymer matrix. Scanning electron microscopy was done to study the surface morphology. Results revealed that more spherical shaped particles with possible aggregation. The highest correlation coefficients were obtained for the Higuchi model, suggesting a diffusion mechanism for the drug release. The results demonstrated that anastrozole nanoparticles with chitosan could be an alternative delivery method for the long-term treatment of breast cancer.

The purpose of the present study was to develop an optimized gastric floating once-daily matrix tablet of ofloxacin (FERMTs) using  hydrophilic polymers such as HPMC K4M, HPMC 100M, isapagulha husk and sodium bicarbonate as buoyancy contributer. The formulation of FERMTs were designed by 23full factorial design taking amount of HPMC K4M, HPMC 100M and sodium bicarbonate as formulation variables and prepared by wet granulation method. The FERMTs were then evaluated for hardness, friability, weight variation, content uniformity, in vitro drug release and floating capacity. Finally, the floating lag time (FLT) and cumulative % drug release at 4h, 8h, 12h and 16h were taken as response variables and the FERMT formulation was numerically optimized by 23full factorial design using Design-Expert software (version 8.1). The optimized formula showed excellent floating efficiency over a 16 h period with FLT of 2.80 mins and drug release over a period of 16 hour. Analysis of dissolution data showed that the kinetic of drug release followed Korsemeyer-peppas model.

Perindopril is an angiotensin converting enzyme inhibitor. The bioavailability of Perindopril following oral administration is 20 % due to high hepatic first pass metabolism. When administered orally, frequent dosing is needed due to its short biological half-life (0.8 to 1hr). sobuccal patches are one of the better option for perindopril administration. 9 Formulations were prepared using 32 full factorial designs by solvent-casting technique to explore the effects of sodium alginate and carbopol 934 (as independent variables) on drug release, mucoadhesive strength and retention time (as dependent variables). The prepared buccal patches were also evaluated for, weight uniformity, patch thickness, folding endurance, surface pH, swelling studies, % moisture content,% drug content, tensile strength, drug release studies, mucoadhesive strength, retention time. The ex-vivo permeation studies were carried out across excised sheep buccal mucosa using modified Franz diffusion cell. Patches exhibited drug release in the range of 70.37to 96.62% in 8 hrs. Drug release from patches followed zero order and higuchi release model and the mechanism of the drug release was due to swelling and erosion of hydrophilic polymers. The formulation was optimized with desirable drug release, mucoadhesive strength and retention time by applying computer software Design Expert 8.0.7.1. Ex-vivo drug release values for the cumulative amount of the drug permeated across the sheep buccal mucosa from optimized formulation was 76.76%. The experimented values were in good agreement with expected values for the optimized formulation which demonstrate the feasibility of the model in the development of buccal patches.

  Formulation and characterization of an ophthalmic delivery system of an antibacterial agent, ofloxacin, based on the concept of pH triggered in situ gelation. Polyacrylic acid (Carbopol 974P) was used as the gelling agent in combination with Noveon® AA-1 USP Polycarbophil as a viscosity enhancer. Formulation optimization was carried out using a 32 full factorial design. The effect of independent variables was evaluated using dependent variables such as gel strength, bioadhesive force, viscosity and in vitro drug release of the formulation. The multiple regression analysis of the results led to equations that adequately describe the influence of the independent variables on the selected responses. Polynomial regression equations and surface plots were used to relate the dependent and independent variables. Furthermore, the desirability function was employed in order to determine the best batch which was then evaluated for in vivo antimicrobial efficacy study, effect of sterilization, ocular irritation study and accelerated stability study. It was found that the optimum values of the responses for pH triggered in situ ophthalmic gel formulation could be obtained at medium levels of Carbopol 974P and Noveon® AA-1 USP Polycarbophil (0.5/0.5%w/w respectively). The formulation retained antimicrobial efficacy, showed insignificant effect over sterilization and found non irritant to the corneal surface confirmed by microscopy of the corneal mucosal membrane compared with reference marketed formulation. The optimized formulation was found to be stable, therapeutically efficacious and providing sustained release of the drug over an 8 h period even after accelerated stability study over three months. The developed system is thus a viable alternative to conventional ophthalmic formulations.   Key words: In situ gelation; Factorial design; Desirability function; Carbopol 974P;Noveon® AA-1 USP Polycarbophil; Ofloxacin