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Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets.
Eur J Pharm Biopharm. 2006 Oct; 64(2):185-92.EJ

Abstract

In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets.

Authors+Show Affiliations

College of Pharmacy, Hebei University, Baoding, PR China. hldrenew@yahoo.com.cnNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

16797948

Citation

Hu, Lian-Dong, et al. "Preparation and in Vitro/in Vivo Evaluation of Sustained-release Metformin Hydrochloride Pellets." European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, vol. 64, no. 2, 2006, pp. 185-92.
Hu LD, Liu Y, Tang X, et al. Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets. Eur J Pharm Biopharm. 2006;64(2):185-92.
Hu, L. D., Liu, Y., Tang, X., & Zhang, Q. (2006). Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets. European Journal of Pharmaceutics and Biopharmaceutics : Official Journal of Arbeitsgemeinschaft Fur Pharmazeutische Verfahrenstechnik E.V, 64(2), 185-92.
Hu LD, et al. Preparation and in Vitro/in Vivo Evaluation of Sustained-release Metformin Hydrochloride Pellets. Eur J Pharm Biopharm. 2006;64(2):185-92. PubMed PMID: 16797948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Preparation and in vitro/in vivo evaluation of sustained-release metformin hydrochloride pellets. AU - Hu,Lian-Dong, AU - Liu,Yang, AU - Tang,Xing, AU - Zhang,Qian, Y1 - 2006/05/10/ PY - 2005/01/26/received PY - 2006/04/27/revised PY - 2006/04/27/accepted PY - 2006/6/27/pubmed PY - 2007/2/10/medline PY - 2006/6/27/entrez SP - 185 EP - 92 JF - European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V JO - Eur J Pharm Biopharm VL - 64 IS - 2 N2 - In this study, metformin hydrochloride (MH) sustained-release pellets were successfully prepared by centrifugal granulation. Seed cores preparation, drug layering, talc modification and coating of polymeric suspensions were carried out in a centrifugal granulator. Talc modification was performed before coating in order to overcome the high water solubility of metformin. The influence of surface modification by talc, the effects of Eudragit types and ratios, as well as the correlation between in vitro release and in vivo absorption were investigated in detail. Experimental results indicated that talc modification made a decisive contribution to controlling the drug release by avoiding drug dumping. Three dissolution media: 0.1 M HCl, distilled water and pH 6.8 phosphate buffer were employed to determine the in vitro release behaviors of the above metformin hydrochloride pellets. The relative bioavailability of the sustained-release pellets was studied in 12 healthy volunteers after oral administration in a fast state using a commercially available immediate release tablet (Glucophage) as a reference. Following coating with a blend of Eudragit L30D-55 and Eudragit NE30D (1:20), at 7% or 10% coating level, respectively (referred to as F-2, F-3), the pellets acquired perfect sustained-release properties and good relative bioavailability. The Cmax, Tmax and relative bioavailability for F-2 and F-3 coated pellets were 1.21 microg/ml, 6 h, 97.6% and 1.65 microg/ml, 8 h, 165%, respectively. Combined use of two Eudragit polymers with different features as coating materials produced the desired results. Restricted delivery of metformin hydrochloride to the small intestine from differently coated pellets resulted in increased relative bioavailability and a sustained release effect. The adoption of several different pH dissolution media established a better relationship between the in vitro release and in vivo absorption of the sustained-release pellets. SN - 0939-6411 UR - https://www.unboundmedicine.com/medline/citation/16797948/Preparation_and_in_vitro/in_vivo_evaluation_of_sustained_release_metformin_hydrochloride_pellets_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0939-6411(06)00088-9 DB - PRIME DP - Unbound Medicine ER -