Preparation and Evaluation of a Sustained Release Formulation of Metoclopramide Hydrochloride HPMC Tablets

Abstract

The objective of the present study was to develop "once daily" sustained release tablets of metoclopramide by direct compression using hydroxypropyl methylcellulose (HPMC). No significant changes in terms of peak shifting, appearance or disappearance of peaks were noted with pure drug, polymers and mixtures. The developed sustained release and marketed immediate release were appraised for physico-chemical parameters such as appearance, weight variation, thickness, hardness, friability and in vitro release study. Developed sustained release tablets of metoclopramide hydrochloride with respect to its physicochemical parameters and drug conent are stable at long term storage conditions at 25 o C and 60% RH,  and accelerated  conditions at 40 o C and 75% RH for a period of  six months. The in vitro release of metoclopramide sustained  release the formulations was compared with the marketed immediate release. The sustained release tablets of metoclopramide were well absorbed and the extent of absorption was higher than that of the marketed tablet. The Cmax and Tmax data showed higher for immediate release compared to sustain release formulation. Developed sustained release demonstrated higher AUC, half-life and lower elimination rate constant values is indicative, that drug leftover in the body for extended period of time and showed signs of prolonged effect. The sustained and efficient drug delivery system developed in the present study will maintain plasma metoclopramide levels better, which resolve the drawbacks related with the conventional therapy. Keywords: Metoclopramide Hydrochloride; Sustained release; Once daily, Hydroxypropylmethyl cellulose; Dissolution study; Pharmacokinetic study. Bu calismanin amaci, hidroksipropil metilseluloz (HPMC) kullanilarak dogrudan sikistirma metoklopramidin surekli olarak birakilan "gunde bir kez" serbest birakilmasidir. Saf ilac, polimerler ve karisimlarda zirveye kayma, gorunum veya piklerin kaybolmasi bakimindan belirgin bir degisiklik kaydedilmedi. Gelistirilmis surekli salim ve pazarlanan derhal salinim, gorunum, agirlik degisimi, kalinlik, sertlik, kirilganlik ve in vitro serbest birakma calismasi gibi fiziko-kimyasal parametreler icin degerlendiirildi. Metoklopramid hidroklorurun fizikokimyasal parametrelerine ve uyusturucu konusuna gore gelistirilmis surekli salinimli tabletleri, 25oC ve% 60RH'de uzun vadeli saklama kosullarinda ve 40oC'de ve% 75 Bagil Nem RH'de, alti aylik bir sure boyunca hizlandirilmis kosullarda kararlidir. Metoklopramidin in vitro salinimi formulasyonlari piyasaya surulen derhal salinimla karsilastirildiginda serbest birakmistir. Metoklopramid'in surekli salim tabletleri iyi absorbe edildi ve emilim derecesi pazarlanan tabletinkinden daha yuksekti. Cmax ve Tmax verileri, surumu serbest birakma formulasyonu ile karsilastirildiginda derhal salinma icin daha yuksek gosterdi. Gelistirilmis surekli salinim, daha yuksek AUC, yarilanma omru ve daha dusuk eliminasyon hizi sabit degerlerinin gostergesi oldugunu ve bu ilacin uzun sure vucutta kalmis oldugunu ve uzun sureli etki belirtileri gosterdigini ortaya koymustur. Bu calismada gelistirilen surekli ve etkin ilac verme sistemi, plazma metoklopramid duzeylerini daha iyi koruyacak ve bu da geleneksel terapi ile ilgili dezavantajlari cozecektir. Anahtar Kelimeler: Metoklopramid Hidroklorur; Surekli serbest birakma; Gunde bir kez, Hidroksipropilmetil seluloz; Erime calismasi; Farmakokinetik calisma.