| Methylphenidate hydrochloride (MPH) is the most commonly prescribed psychoactive drug in children for the treatment of attention deficit hyperactivity disorder (ADHD).MPH is rapidly absorbed and bioavailability is low (approx.30%) following oral administration.We developed methylphenidate hydrochloride hydrophilic transdermal therapeutic system(TTS). TTS offer many advantages over the conventional dosage forms, including constant blood levels, avoids first-pass metabolism, increased compliance. In this paper, the transdermal characteristic of MPH and MPH-TTS were studied .MPH across hairless mouse skin was studied with Franz diffusion cell. The PBS with pH6.8 was used as permeation medium. A high performance liquid chromatographic (HPLC) method was established to determine the concentration of MPH in vitro. The linear range was 0.5-800 g .ml-1 (r=0.9999) .The steady state flux (J) and permeability coefficient(P) of MPH was investigated with different drug contents. The permeability coefficient (P) and enhancement ratios (ER) for MPH through the hairless mouse skin being treated by variable enhancers were compared with control. The penetration of MPH through hairless mouse skin was clear enhanced by 8% Azone and 5% propylene glycol, The enhancement ratio was 4.20 and 6.17 respectively.Adhesion properties were evaluated by means of Peel adhesion 180 test, creep resistance test and rolling ball test.This study was performed on two series of MPH transdermal patches in which the pressure sensitive adhesive was made of hydrophilic matrices and lipophilic matrices. Methacrylic esters, polyisobutylene, silicon were compared as the lipophilic matrices. With acrylic polymers Eudragit L100 as adhesive vehicle, the formulation and procedure of MPH hydrophilic matrices patch (MPH-E100-TTS) was studied. The hydrophilic matrices TTS was prepared using Eudragit L100 polymer(MPH-L100-TTS). Relation the polymethyl methacrylate (Eudragit LI00) and the plasticizer were investigated though cellulose, PVP, PVA and Carbopol. Moreover, optimal formulation was achieved by orthogonal experiment with the permeability of the drug across the hairless mouse skin and adhesion of the patch as index of the optimization. The methodology for determination the quality of patch such as adhesion, content, release and permeation were studied. The DSC technique was used to study the contraindication between the drug and excipients and it is showed they were compatible with each other. It was showed that the permeation kinetics of MPH across the hairless mouse skin belonged to zero-order pattern.The contents of MPH-TTS is 1.66mg cm2. MPH-E100-TTS was single layer matrices type, that values of J, LT, peel adhesion, creep resistance were 36.68 u g-cm~2-h"', 0.15h, 91.46 cN-cm"1, 65min. MPH-L100-TTS also was single layer matrices type., that values of J, LT, peel adhesion, creep resistance were 31.85u g-cm-2-h"1, 0.30h, 88.23 cN cm"1, 280min. The percutaneous test In vitro, The cumulative release of was 78.99% and 60.96% respectively. Both of TTS were skin control types. In vitro kinetics of MPH across hairless mouse skin can be described bi Higuchi equation.We chose the system contained of isopropyl/water/lecithin/alcohol according to the phase diagram. We prepared the MPH W/O microemulsion and studied percutaneous absorption of microemulsion across hairless mouse skin. Values of J, mean droplet diameter, conductance, refractive were 43.43 u g cm" h"1, 14.28nm, 0.68 102 u s cm"1, 1.4170. The penetration of drug through hairless mouse skin was clear enhanced by microemulsion. (PO.01)A HPLC/MS/MS method was established to determine the plasma concentration .The linear range was 0.2-500ng ml"1(r=0.9995). The limit was O.OSng. The pharmacokinetic study was carried out in rabbits. MPH-L100-TTS, MPH tablets, MPH intravenous injection was single administrated respectively. The blood concentration-time curve of MPH-L100-TTS was gently and provided a stable level in 48h. It is showed that the therapeutic effect of MPH-L100-TTS prolongedcom...
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