Design and Evaluation of An Extended-Release Olmesartan Tablet Using Chitosan/Cyclodextrin Composites

Abstract

Sustained-release olmesartan tablets (OLM) were prepared by the simple, direct compression of composites of anionic sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and cationic spray-dried chitosan (SD-CS), and were evaluated for use as a sustained release preparation for the treatment of hypertension. An investigation of the interaction between OLM and SBE-β-CD by the solubility method indicated that the phase diagram of the OLM/SBE-β-CD system was the AL type, indicating the formation of a 1:1 inclusion complex. The release of OLM from tablets composed of the SD-CS/SBE-β-CD composite was slow in media at both pH 1.2 and at 6.8. The in vitro slow release characteristics of the SD-CS/SBE-β-CD composite were reflected in the in vivo absorption of the drug after normal rats were given an oral administration of the preparation. Furthermore, the SD-CS/SBE-β-CD composite continuously increased the antihypertensive effect of OLM in hypertensive rats, compared with that of the drug itself. These results suggest that a simple mixing of SD-CS and SBE-β-CD can be potentially useful for the controlled release of a drug for the continuous treatments of hypertension.

Host–Guest Interaction Study of Olmesartan Medoxomil with β-Cyclodextrin Derivatives

“…Olmesartan medoxomil (OLM), 1a) is an angiotensin II receptor type 1 blocker used for the treatment of hypertension [28,29]. OLM also has antioxidant activity and a renal protective effect that is independent of its antihypertensive effect [28,30].…”

“…Olmesartan medoxomil (OLM), 1a) is an angiotensin II receptor type 1 blocker used for the treatment of hypertension [28,29]. OLM also has antioxidant activity and a renal protective effect that is independent of its antihypertensive effect [28,30]. OLM is a prodrug that is hydrolyzed into its active form, olmesartan, during absorption from the gastrointestinal tract [31,32].…”

“…(a) (b) Several approaches have been explored to improve the dissolution rate and bioavailability of OLM, including the formulation of the self-microemulsifying drug delivery system (SMEDDS) with Acrysol EL135 as oil, Tween 80 as surfactant and Transcutol P as co-surfactant [31], ternary solid dispersion of the drug with hydroxypropyl-β-cyclodextrin (HP-β-CD) and N-methyl-D-glucamine (MG) prepared by mechanochemistry [33], nanosized formulation as lipid-based nanoparticles and nanosuspension [29] and sustainedrelease tablets using composites of anionic sulfobutyl ether-β-cyclodextrin (SBE-β-CD) and cationic spray dried chitosan (SD-CS) [28].…”

“…Complexation of active pharmaceutical ingredients with CD is one of the valuable strategies used to enhance the solubility of poorly water-soluble drugs, the dissolution rate, and consequently their bioavailability [28,34]. Thakkar et al [35] have investigated the inclusion of OLM in HP-β-CD cavity and reported significantly higher saturation solubility, dissolution rate, and intestinal permeation for OLM/HP-β-CD binary systems.…”