Formulation and In Vitro, In-Vivo Evaluation of Floating Bilayer Tablets of Ezetimibe- Nateglinide

Abstract

In this research work, nateglinide, ezetimibe was selected as model drugs. Nateglinide is an amino acid derivative that induces an early insulin response to meals decreasing postprandial blood glucose levels which act by binding to β cells of the pancreas to stimulate insulin release. Ezetimibe is a lipid-lowering compound that inhibits intestinal cholesterol and phytosterol absorption. Formulation of sustained release floating bilayer tablets of ezetimibe-nateglinide with Polyox WSR 303, Carbopol 934P, HPMC K4M, Na CMC. The compatibility of nateglinide and excipients used in study was determined using DSC and this study revealed that no interaction between drug and excipients used in the formulation. The optimized nateglinide-ezetimibe floating formulations (NGT3, NGT10) showed satisfactory results with respect to in vitro buoyancy and sustained drug release and was physically stable for 3 months period. The vivo radiographic studies showed that the BaSO4-loaded floating tablets were retained in the stomach for 4.16 ± 1.57 h (n=3).

Introduction

Bilayer tablet is suitable for sequential release of two drugs in combination, separate two incompatible substances and for sustained release tablet in which one layer is immediate release as initial dose and second layer is maintenance dose. In which the one layer is formulated to obtain immediate release of the drug, with the aim of reaching a high serum concentration in a short period of time. The second layer is a controlled release, which is designed to maintain an effective plasma level for a prolonged period. The pharmacokinetic advantage relies on the fact that drug release from fast releasing layers leads to a sudden rise in blood concentration. However, the blood level is maintained at steady state as the drug is released from the sustaining layer.

One of the most feasible approaches for achieving prolonged and predictable drug delivery profiles in gastrointestinal tract is to control the gastric residence time (GRT) using gastroretentive dosage forms that offer a new and better option for drug therapy. Dosage forms that can be retained in the stomach are called gastroretentive drug delivery systems (GRDDS). Gastroretentive floating drug delivery system was first described by Davis in 1968. Over the last two decades, numerous GRDDS have been designed to prolong gastric residence time (Talukder and Fassihi, 2004a). Figure 1.3 describes how the drug absorption takes place in the case of conventional dosage forms and GRDDS. GRDDS can improve the controlled delivery of drugs that have an absorption window. This system releases the drug continuously for a prolonged period of time before it reaches its absorption site, thus ensuring its optimal bioavailability (Brahma and Know, 2000).

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Materials

Nateglinde was collected as a gift sample from splendid pharma, Ltd, Puna, Ezetmibe collected from Hetero drugs Ltd, Hyderabad. Hydroxy propyl methylcellulose (HPMC K4M) and Polyox WSR 303 were received as gift samples from Orchid pharma Ltd., Chennai, India. Sod.CMC and Carbopol 971P were received from M/s Aurobindo Pharma. Ltd., Hyderabad, India. Sodium bicarbonate, magnesium stearate and talc were purchased from S.D. FineChem. Ltd., Mumbai, India. Acetonitrile and methanol HPLC grade were purchased from Sigma Aldrich chemicals Dombivli, India. All other solvents and reagents used were of analytical grade.

G. Nagaraju, V. Sirisha, Kavati.Ramakrishna, Hareesh Dara, Formulation and In Vitro, In-Vivo Evaluation of Floating Bilayer Tablets of Ezetimibe- Nateglinide, January 2019, DOI:10.21276/ijpbs.2019.9.1.206, International Journal of Pharmacy and Biological Sciences-IJPBSTM (2019) 9 (1): 1579-1591, Online ISSN: 2230-7605, Print ISSN: 2321-3272, Received: 12 Oct 2018 / Accepted: 8 Nov 2018 / Published online: 1 Jan 2019