Design and Evaluation of Losartan Potassium Effervescent Floating Matrix Tablets: In Vivo X-ray Imaging and Pharmacokinetic Studies in Albino Rabbits.

Mohamed Rahamathulla,Sultan Alshehri,Faiyaz Shakeel,Abdullah Alshetaili,Umme Hani,Srinivasan Saisivam,Mohammed M Ghoneim,Hosahalli Veerabhadrappa Gangadharappa

doi:10.3390/polym13203476

Abstract

Losartan potassium (LP) is an angiotensin receptor blocker used to treat hypertension. At higher pH, it shows poor aqueous solubility, which leads to poor bioavailability and lowers its therapeutic effectiveness. The main aim of this research was to develop a direct compressed effervescent floating matrix tablet (EFMT) of LP using hydroxyl propyl methylcellulose 90SH 15,000 (HPMC-90SH 15,000), karaya gum (KG), and an effervescent agent, such as sodium bicarbonate (SB). Therefore, an EFMT has been developed to prolong the stomach residence time (GRT) of a drug to several hours and improve its bioavailability in the stomach region. The blended powder was evaluated for pre-compression characteristics, followed by post-compression characteristics, in vitro floating, water uptake studies, and in vitro studies. The optimized formulation of EFMT was investigated for in vivo buoyancy by X-ray imaging and pharmacokinetic studies in Albino rabbits. The results revealed that the parameters of pre- and post-compression were within the USP limits. All tablets showed good floating capabilities (short floating lag time <1 min and floated for >24 h), good swelling characteristics, and controlled release for over 24 h. The Fourier-transform infrared (FTIR) and differential scanning calorimetry (DSC) spectra showed drug–polymer compatibility. The optimized formulation F3 (HPMC-90SH 15,000-KG) exhibited non-Fickian diffusion and showed 100% drug release at the end of 24 h. In addition, with the optimized formulation F3, we observed that the EFMT floated continuously in the rabbit’s stomach area; thus, the GRT could be extended to more than 12 h. The pharmacokinetic profiling in Albino rabbits revealed that the relative bioavailability of the optimized LP-EFMT was enhanced compared to an oral solution of LP. We conclude that this a potential method for improving the oral bioavailability of LP to treat hypertension effectively.

Highlights

In the drug delivery system, the oral route has been the most popular and widely used route of administration
Based on in vivo studies via X-ray imaging in Albino rabbits, the formulation F3 exhibited the floatability of the tablet in the stomach and extended the gastric residence time (GRT) to around 12 h
Floating tablets might successfully be utilized to regulate the release of Losartan potassium (LP), which has a narrow absorption window in the upper part of the gastrointestinal tract (GIT) or stomach

Summary

Introduction

In the drug delivery system, the oral route has been the most popular and widely used route of administration. Due to the irregular and changing environment in the gastrointestinal tract (GIT), the traditional per oral dosage forms cannot provide prolonged effective plasma drug concentration and bioavailability. This is due to several physiological difficulties/limitations, such as gastric emptying (GE), stomach pH, gastric motility (GM), gastric residence time (GRT), and so on; this can be resolved by formulating a suitable dosage form [1]. The therapeutic level is kept constant through continuous drug release This can increase patient compliance by lowering the frequency of dose; drugs with shorter half-lives can produce a significantly better therapeutic effects. One of the most prevalent types of GRDDS is the floating/pulsatile drug delivery system (FDDS/PDDS), which increases the drug absorption by extending the GRT within the upper GIT (effervescent or non-effervescent) [3,4,5,6]

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