Potential Use of Polyvinyl Acetate–Polyvinylpyrrolidone Mixture for the Development of Atenolol Sustained Release Matrix Tablets: Optimization of Formulation through <i>in Vitro</i>–<i>in Vivo</i> Assessment Study

Abstract

The objective of this study was to develop sustained release matrix tablets of atenolol (AT) using different concentrations of polyvinyl acetate-polyvinylpyrrolidone mixture (KSR) (20, 30, or 40%) with various types of fillers such as spray dried lactose (SP.D.L), avicel pH 101 (AV), and emcompress (EMS). The physical characteristics of the prepared tablets were evaluated. Characterization of the optimized formulation was performed using Fourier transform (FT)-IR spectroscopy and differential scanning calorimetry (DSC). Moreover, the in vitro release profiles of AT formulations were investigated in different pH dissolution media. Drug release kinetics and mechanisms were also determined. The results revealed that there was no potential incompatibility of the drug with the polymer. The release profiles of AT were affected by the concentration of KSR, fillers used, and pH of the dissolution media. The drug release kinetic from most of the formulations obeyed Higuchi diffusion model. The selected formulae were investigated for their stability by storage at 30 and 40°C with atmospheric humidity and 75% relative humidity (RH), respectively. The results demonstrated that no change in the physicochemical properties of the tablets stored at 30°C/atmospheric RH in comparison with some changes at 40°C/75% RH. Finally, the in vivo study provided an evidence that the optimized AT tablet containing 40% KSR and SP.D.L exhibited prominent higher oral bioavailability and more efficient sustained-release effect than the drug alone or the commercial tablet product. It is noteworthy that KSR could be considered as a promising useful release retardant for the production of AT sustained release matrix tablets.Key words polyvinyl acetate-polyvinylpyrrolidone mixture; atenolol; sustained; tablet; stability; bioavailability Atenolol (AT) is a selective β1 receptor blocker that decreases blood pressure primarily by reducing cardiac output. It may also reduce sympathetic outflow from the central nervous system (CNS) and prevent the release of renal renin, thus reducing angiotensin II formation and aldosterone secretion. 1)About 50% of an oral dose of AT is absorbed. Peak plasma concentrations are reached in 2 to 4 h. The plasma half-life is about 6 to 7 h. AT has little or no hepatic metabolism and the renal system is considered the main site of its excretion. 2)Administration of conventional tablets of AT has been reported to show fluctuations in the plasma drug concentration leading to the increase in its side effects or decrease in its concentration at receptor site. [3][4][5] To overcome such problems, sustained release matrix tablets containing AT were developed in order to maintain proper blood level for a long time without fluctuation. [6][7][8]

Bioequivalence Study of Atenolol Tablets in Healthy Chinese Subjects Under Fasting and Fed Conditions

“…[6][7][8] Furthermore, it may decrease sympathetic outflow from the central nervous system and prevent the release of renin from the kidneys, thereby decreasing the formation of angiotensin II and secretion of aldosterone. 9,10 After oral administration, the bioavailability of atenolol is approximately 50%. 4,8,11 Furthermore, peak plasma concentrations are reached in 2-4 hours, with a plasma half-life of approximately 6-7 hours.…”

“…4,8,11 Furthermore, peak plasma concentrations are reached in 2-4 hours, with a plasma half-life of approximately 6-7 hours. 9 Less than 10% of atenolol is metabolized by the liver, with approximately 85%-95% being excreted unchanged in the urine. 12 Therefore, the urinary system is considered the primary excretion site.…”

“…12 Therefore, the urinary system is considered the primary excretion site. 9,13 Atenolol may be used alone or concomitantly with other antihypertensive agents, including thiazide-type diuretics, hydralazine, prazosin, and α-methyldopa. 11,14 To date, the pharmacokinetics (PK) and bioequivalence (BE) of atenolol have not been comprehensively studied in healthy Chinese volunteers.…”

“…Atenolol, or 4‐(2‐hydroxy‐3‐isopropyl‐aminopropoxy) phenylacetamide, is a cardioselective β 1 ‐blocker that primarily decreases blood pressure by decreasing cardiac output 6–8 . Furthermore, it may decrease sympathetic outflow from the central nervous system and prevent the release of renin from the kidneys, thereby decreasing the formation of angiotensin II and secretion of aldosterone 9,10 . After oral administration, the bioavailability of atenolol is approximately 50% 4,8,11 .…”

Mikroenkapsulasi atenolol dengan penyalut hidroksipropil metilselulosa (HPMC) menggunakan metode emulsifikasi penguapan pelarut

“…Penurunan laju pelepasan atenolol dari mikrokapsul disebabkan hidroksipropil metilselulosa membutuhkan waktu untuk mengembang dalam air dan zat aktif akan mengalami difusi untuk keluar dari mikrokapsul setelah zat aktif terdisolusi dalam media disolusi. 18 Data disolusi tersebut belum bisa mewakili pelepasan atenolol keseluruhan karena penggunaan medium disolusi belum mewakili keseluruhan saluran gastrointestinal yaitu lambung dan usus. Selain itu, seharusnya disolusi dilakukan selama 24 jam untuk melihat bagaimana profil pelepasan atenolol dari mikrokapsul.…”