factorial design

The target of the present study is to use experimental design in screening and optimizing experimental variables to develop a spectrophotometric method for determination of Cefdinir (CFN) antibiotic. The proposed method is based on the oxidative coupling reaction of CFN with 3-methylbenzothiazolinone-2- hydrazone (MBTH) in presence of FeCl3 in acidic medium forming a green colored chromogen measured at λ max of 660 nm. A 25-2 fractional factorial design was utilized to screen the effect of FeCl3, HCl and MBTH concentrations, in addition to reaction time and nature of diluting solvent on the absorbance of the formed chromogen. One way ANOVA and Pareto ranking analyses have shown that all variables were statistically significant. Full factorial design was then utilized to evaluate the effects of the variables on the selected response. With the help of a response surface and contour plots the optimum value of each variable was determined and used for further experiments. These optimum values were 5mg/mL FeCl3, 0.06% HCl, 4mg/mL MBTH, reaction time of 10 min and methanol as diluting solvent. Beer’s law is obeyed in the range of 0.5-6.0 μg/mL. The proposed method was successfully applied for the determination of CFN in bulk powder and commercial dosage forms without interference from the commonly encountered excipients and additives. The mean recoveries of the analyte in pharmaceutical preparations were in agreement with those obtained from a comparison method, as revealed by statistical analysis of the obtained results using the Student's t-test and the variance ratio F-test.

Verapamil hydrochloride has a short half-life 2.8 to 7.4 hours, a narrow absorption window and is mainly absorbed in proximal areas of GIT. The present investigation aimed to formulate a floating drug delivery system of Verapamil Hydrochloride by Quality by design approach. In risk assessment, the effects of process and formulation variables on particle drug release and floating lag time were investigated. Design of experiments (DoE) and multivariate data analysis were used to identify important process and formulation parameters. A 22 factorial design in replicate was employed to produce controlled release floating tablet. The effect of critical formulation variables i.e. levels of HPMC K15M and gas generating agent (i. e. Sodium bicarbonate and citric acid) on % Drug release after 12 hr (% DRel12) and floating lag time (FLT) were analyzed. Verapamil HCl tablets were evaluated for hardness, friability, weight variation, drug content, floating behavior and drug release studies were conducted in 0.1 N HCl (pH 1.2) at 37 ± 0.5OC. The tablets showed acceptable physicochemical properties. The two independent variables studied exhibited a significant influence (P < 0.05) on % DR 12 Hr and FLT. Numerical and graphical optimization technique employing design space approach was used to develop a new formulation by setting constrains on the dependent and independent variables. The experimental values of % DR 12 Hr and FLT for optimized batch were found to be in close agreement with those predicted by mathematical model. Experimental values obtained from the optimized formulations were in both cases close to the predicted values, thus confirming the validity of the generated mathematical model. These results demonstrated the effectiveness of the proposed floating tablet, as well as the usefulness of the QbD approach for the development of Verapamil floating tablet with optimized properties.

This  study was  focused over  the  designing  of sustained  release  HPMC  K100M  micropellet dosage form for  Ibuprofen which is an anti-inflammatory agent and broadly used for treating mild and severe pains. The approach of this study was to make a comparative evaluation among polymers  &  excipients  and  to  assess  the  effect  of  physicochemical  nature  of  the  active ingredients on the drug release profile. The prototype micropellets were obtained using drum pelletizer at 300 rpm. Percentage of water in binding liquid, i.e. IPA, is varied from 95 to 99% and  the effect  over  various parameters,  such as  particle size,  entrapment,  bulk  density and particle  shape,  were observed. Concerning the results of prototype preparation of Ibuprofen micropellets  were  prepared  using  HPMC  K100M,  as  release  retardant,  in  three  different concentrations i.e. 16.7%, 33.3% & 50%. Formulated micropellets showed particle size in the range of 275-284µm, bulk density (0.74-0.82 g/ml), % yield (25.9 -58.3%) & % entrapment (32.8-34.3%). Formulations showed the   maximum   desirability 0.996. Dry suspension formulation  parameters  such  as  pH  (5.15),  Viscosity  (450  cps),  Redispersibility  (5)  & Sedimentation volume (0.46 ml), was  found in  range. Formulation           PIH   were selected as the best   optimized  formulation  and  evaluated  for  In-vivo  parameters,  results  inferred  good sustainability with p>0.0001. Formulated micropellet showed sustained in-vitro dissolution rate, due to optimized polymer concentration. The micropellets were stable at 40°C±2°C/75%±5% RH as per ICH guidelines, after 3 months.

Conventional liquid ophthalmic formulations are most convenient from patient point of view. But these formulation shows low bioavailability because of a constant lachrymal drainage in the eye which leads to frequent dosing. Moreover, the absorption of the drug drained through the nasolacrymal duct may result in undesirable side effects. To overcome these limitation different approaches has been applied such as ointment, gel, cream etc. These ophthalmic formulations also fails to show desired therapeutic responses because of their own disadvantages such as ointment makes blurred vision. So two different systems was combined together as niosomes and in-situ gel by incorporating niosomes in in-situ gel formulation so that it is easy to administered and retain at the site for prolong period of time. The Ofloxacin (OFL), a second generation fluoroquinolone derivative used in eye infections needs frequent dosing in its solution form. Vesicular system reported prolonged and controlled action at corneal surface but it has again limitation of drainage along tear produced.  In this, first niosomes containing ofloxacin were prepared by applying 32 full factorial designs and evaluated for its vesicle size, percent entrapment, in-vitro drug release kinetics and their stability. Also in-situ gel formulation was prepared by dispersing the niosomes in solution of carbopol 940 and Hydroxy Propyl Methyl Cellulose (HPMC) K4M. In-vitro drug release kinetics from niosomal in-situ gel formulation indicates that the minimum inhibitory concentration (MIC) of drug (4 μg/ml) was achieved within 1-2 hrs (batch G1-G9).

Isoxsuprine hydrochloride, a β2 agonist used in peripheral vascular disease was formulated into sustain release matrix tablets, by wet granulation method using HPMC K15M as release retardant in different proportions and PVP K25 as a binder. The parameter optimized using 32 factorial designs. The tablets of all batches were evaluated for drug content, hardness, friability, weight variation and in vitro drug release profile. The dissolution profiles of formulated tablets were compared with a marketed product. The similarity factor (f2) was calculated to check the similarity with marketed product. Different dissolution models were applied to drug release data in order to evaluate release mechanisms and kinetics. Mathematical treatment of the in vitro drug release data suggests that, the drug release of all the formulations exhibited nearly zero-order kinetics, the release exponent n ranged from 0.69 to 0.8 indicate that drug release from the all batches occurred by non-Fickian diffusion mechanism (anomalous transport), i.e. the release is ruled by both diffusion of the drug and dissolution of the polymer. According to SUPAC guidelines the formulation containing combination of 25% HPMC K15M and 10% PVP K25 is the most similar formulation to marketed product.