ABSTRACT
The objective of this present study was to develop and evaluate transdermal films of alfuzosin hydrochloride for controlled release at a predetermined rate over a prolonged period of time and assessment of film forming ability Cordia dichotoma fruit mucilage using alfuzosin as drug of choice. The films of alfuzosin were prepared by solvent evaporation technique. The formulations, from F1 to F3 contain Cordia dichotoma fruit mucilage (CDFM; 8%, 12% and 16%) and the formulations, from F4 to F6 contain CDFM along with sodium alginate (125 mg, 150 mg and 175 mg). Glycerin and propylene glycol were used as plasticizer; span-80 used as permeation enhancer; methyl paraben and propyl paraben were used as preservatives (in case of plant mucilage as polymer) in all the formulations. Fourier transform infra red spectral analysis studies showed that there is no drug polymer incompatibility. The films of alfuzosin were prepared by using different polymers such as C. dichotoma and also in combination with sodium alginate that had shown good results for all the evaluated parameters within the range. In vitro drug release studies had shown that the maximum release of drug was observed for F3 formulation was 91.87 ± 1.34 at 24 hrs and F6 formulation was 99.62 ± 0.14 at 24 hrs. The concentration of CDFM is increased from 8% to 16% that leads to enhancement of dissolution rate. In-vitro drug release studies of optimized formulations, F3 formulation followed first order and F6 formulation followed zero order kinetics. The obtained results were concluded that CDFM have good film forming ability alone and combination with sodium alginate.
ABSTRACT
Purpose: The main objective of the investigation was to develop a transdermal therapeutic system for alfuzosin hydrochloride and to study the effects of polymeric system and loading dose on the in vitro skin permeation pattern. Materials and methods: Principles of experimental design have been exploited to develop the dosage form. Ratio of ethyl cellulose (EC) and polyvinyl pyrrolidone (PVP) and loading dose were selected as independent variables and their influence on the cumulative amount of alfuzosin hydrochloride permeated per cm2 of human cadaver skin at 24 h (Q24), permeation flux (J) and steady state permeability coefficient (P SS) were studied using experimental design. Various physicochemical parameters of the transdermal films were also evaluated. Activation energy for in vitro transdermal permeation has been estimated. Results: Ratio of EC and PVP was found to be the main influential factor for all the dependent variables studied. Drug loading dose was also found to influence the dependent variables but to a lesser extent. Physicochemical parameters of the prepared films were evaluated and found satisfactory. Activation energy for alfuzosin permeation has also been estimated and reported. Conclusion: The therapeutic system was found to be dermatologically non-irritant and hence, a therapeutically effective amount of alfuzosin hydrochloride can be delivered via a transdermal route.
Subject(s)
Animals , Humans , Rabbits , Adrenergic alpha-1 Receptor Antagonists/administration & dosage , Drug Delivery Systems/methods , Quinazolines/administration & dosage , Administration, Cutaneous , Cadaver , Permeability , Skin Absorption , ThermodynamicsABSTRACT
OBJECTIVE:To compare the bioequivalence between alfuzosin hydrochloride sustained release tablets and the imported alfuzosin common tablets.METHODS:20 health volunteers were assigned to receive oral single dose of 5mg sustained-release and imported tablets of alfuzosin by self crossover way,with alfuzosin concentration in serum determined by HPLC.The pharmacokinetic parameters were calculated;the statistical analysis was carried out and the bioequiavailability was evaluated.RESULTS:The main pharmacokinetic parameters of the sustained-release and the imported tablets of alfuzosin were as follows:Cmax:(28.92? 9.63) ?g? L-1 vs.(32.92? 10.23) ?g? L-1;tmax:(2.7? 0.6) h vs.(1.4? 1.0) h;AUC0～ ∞:(221.14? 59.46) ?g? h? L-1 vs.(245.68? 67.20) ?g? h? L-1;t1/2:(6.68? 0.85) vs.(4.73? 1.22) h;AUC0～ 24:(215.20? 49.63) vs.(226.30? 53.60) ?g? h? L-1.The relative bioavailability of alfuzosin hydrochloride sustained release tablets was(92.2? 13.2) %.CONCLUSION:The 2 preparations of alfuzosin are bioequivalent.