ONE FACTOR RESPONSE SURFACE METHODOLOGY (RSM) FOR THE OPTIMIZATION OF ORAL VENLAFAXINE HCL CONTROLLED RELEASE ORGANOGEL

Objective: The aim of this study was to develop the oral Venlafaxine HCl controlled-release organogel (organogel–CR) by using one-factor response surface methodology (RSM). Methods: In this study, Drug-excipient compatibility was evaluated by FT-IR. A total of 14 experimental runs were carried out employing the detailed conditions designed by a single factor completely randomized design based on the response surface methodology was used to check the concentration effect of 12-Hydroxy stearic acid (12-HSA) at different cooling rates on drug release at 10 h (Q10) and after 12 h (Q12). Multiple linear regression analysis, analysis of variance (ANOVA) and graphical representation of the influence factor were performed by using design expert 12. The developed organogel was also evaluated for viscosity, strength, transition temperature, diffusivity and Scanning electron microscopy (SEM). Prepared organogel was filled in the capsule and investigated for weight variation, drug content, erosion of organogel and In vitro drug release study. Results: FT-IR results showed that there was no chemical interaction between the drug and excipients. The SEM photograph indicates that the developed organogel was highly viscous with 3D network structure. The experimental confirmation tests showed a correlation between the predicted and experimental responses (R2 = 0.9937 and 0.9709). The results of ANOVA suggested that calculated F values of all dependent variables are greater than tabulated values. The optimal point obtained was located in the valid region and the optimum in vitro release of the predicted batch containing 7.9% concentration of 12-HSA with gradual cooling rate. To validate the evolved mathematical models, a checkpoint was selected and its desirability value was found to be 0.866. Conclusion: Oral controlled release Venlafaxine HCl organogel fix the problem of repeated dosing and patient noncompliance

PART I: OPTIMIZATION OF HYDRALAZINE HYDROCHLORIDE IMMEDIATE RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET

Objective: Aim of the present study was the optimization of the immediate release (IR) layer containing hydralazine hydrochloride (HHC) 25 mg and compressed with a sustained-release (SR) layer of isosorbide dinitrate (ISDN) 40 mg to decrease the dosing frequency. Methods: In this study, Drug-excipients compatibility study was carried out by FT-IR and a preliminary trial was conducted for screening of super disintegrating agents. The amount of sodium starch glycolate (SSG) (X1) and the amount of ac-di-sol® (X2) was chosen as independent variables in 32 full factorial design while wetting time (WT) (Y1), disintegration time (DT) (Y2) and In vitro drug release at 15 min (Q15) (Y3) were taken as dependent variables. Multiple linear regression analysis, ANOVA, and graphical representation of the influence of factor by 3D plots were performed by using sigma plot 13.0. In the present study, the following constraints were used for the selection of an optimized batch: WT<16 s, DT<25 s, and Q15>90%. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value. Results: FT-IR spectra show that the drug and excipients were compatible with each other. The calculated F values found for WT, DT, and Q15 were 045.559, 077.100 and 278.760, respectively. All Calculated F values are greater than tabulated values for all dependent variables. Prepared checkpoint was selected from its desirability value 0.935 and it gives a 100% drug release within 30 min. Conclusion: These results confirm that the prepared HHC 25 mg IR layer is used for rapid control of hypertension

PART II: OPTIMIZATION OF ISOSORBIDE DINITRATE SUSTAINED RELEASE LAYER IN ANTIHYPERTENSIVE BILAYER TABLET

Objective: Aim of the present study was the optimization of the sustained release (SR) layer of isosorbide dinitrate (ISDN) 40 mg and compressed with the immediate-release (IR) layer of hydralazine hydrochloride (HHC) 25 mg to decrease the dosing frequency and development of a novel b. i. d dosage form. Methods: Drug excipients compatibility study was carried out by FT-IR and a preliminary study was conducted for screening of polymer. The amount of HPMC K100M (X1) and the amount of Polyoxtm WSR303 (X2) were chosen as independent variables in 32full factorial designs. While % cumulative drug releases at 1 h (Q1) (Y1), % cumulative drug release at 2 h (Q2) (Y2), % cumulative drug release at 4 h (Q4) (Y3) and % cumulative drug release at 6 h (Q6) (Y4), were taken as dependent variables and statistically evaluation by using sigma plot 13.0. In the present study, according to the U. S. P. 2007 the following constraints were used for the selection of an optimized batch: Q1=15% to 30%, Q2=50% to 70%, Q4=65% to 85% and Q6>75%. To validate the evolved mathematical models, a checkpoint batch was selected from its desirability value. Results: FT-IR spectra show that the drug and excipients were compatible with each other. The calculated F values found for Q1, Q2, Q4, and Q6 were 084.583, 038.188, 057.719, and 118.396, respectively. All Calculated F values are greater than the tabulated value for all dependent variables. Prepared checkpoint batch selected from its desirability value 1 and it gives a 93.40±1.29 % drug release within 6 h. Conclusion: This bilayer formulation of anti-hypertensive drugs decreases the dosing frequency of HHC and ISDN

Main steps in DNA double-strand break repair: an introduction to homologous recombination and related processes

ISSN:0009-5915ISSN:1432-088