Comparative Analysis of the Release Performance of Indomethacin From Transdermal Therapeutic Systems

Abstract

By their advantages, transdermal therapeutic systems (TTSs) represent an alternative to the conventional pharmaceutical forms. In this study, 3 formulations of TTSs with indomethacin (IND) were developed, which were subjected to analysis by model-independent (by calculation of the f1 and f2 factors; linearization by simple regression), respectively model-dependent methods (modelling with Higuchi function). Release evaluation of the IND was performed using the Franz diffusion cell method through a synthetic or biological membrane, at pH 5.5 and pH 7.4. The obtained results showed that although differences were observed between the analysed release profiles, at an evaluation of the f2 factors there were observed similarities in the shapes of the release curves. By simple linear regression it was determined the diffusion flux through the membranes, which varied depending on the pH and on the type of membrane: 0.749-80.270 g/cm 2 h. The R² < 1 values denote the influence of the ingredients in the IND release. Under certain experimental conditions, the IND3 formulation maintains the steady state for 28 hours at pH 5.5, respectively 12 hours at pH 7.4. Rezumat Datorită avantajelor pe care le conferă, sistemele terapeutice transdermice (STT) reprezintă o alternativă la formele farmaceutice convenţionale. În acest studiu s-au dezvoltat 3 formulări de STT cu indometacin (IND), care au fost supuse analizei prin metode model-independente (calcularea factorilor f1 și f2; liniarizarea prin regresie simplă), respectiv modeldependente (modelare cu funcția Higuchi). Evaluarea cedării IND s-a realizat prin metoda cu celula difuzimetrică Franz, studiul efectuându-se prin membrană sintetică sau biologică, la pH 5,5 și pH 7,4. Rezultatele obținute au arătat că deși au fost observate diferenţe între curbele de cedare analizate, la o evaluare a factorilor f2 s-a observat o similaritate în alura curbelor de cedare. Prin liniarizarea prin regresie simplă s-a determinat fluxul prin membrane, care a variat în funcţie de pH şi de tipul membranei: 0,749-80,270 g/cm 2 h. Valorile R² < 1 denotă influenţa ingredientelor în cedarea IND. În anumite condiții experimentale, formularea IND3 menține starea de echilibru 28 ore la pH 5,5, respectiv 12 ore la pH 7,4.

Applying the Principles of Quality by Design (Qbd) Coupled With Multivariate Data Analysis (Mvda) in Establishing the Impact of Raw Material Variability for Extended Release Tablets

“…Viscosity is a reflection of molecular weight and molecular weight distribution, while the substitution affects the hydrophobic/hydrophilic status of the material. The %HP attributes hydrophilicity, improving hydration/gel formation, while viscosity influences the gel strength in relation to diffusion [1,2,4,48]. The effect of particle size is debatable, but some studies suggest that it may affect the gel quality [19].…”