Novel Gastroretentive Sustained-release Tablet of Tacrolimus Based on Self-microemulsifying Mixture: in Vitro Evaluation and in Vivo Bioavailability Test

Overview

Journal Acta Pharmacol Sin

Specialty Pharmacology

Date 2011 Sep 20

PMID 21927013

Citations 7

Authors

Yan-Ping Wang

Yong Gan

Xin-Xin Zhang

Affiliations

Soon will be listed here.

Abstract

Aim: To develop a novel gastroretentive drug delivery system based on a self-microemulsifying (SME) lipid mixture for improving the oral absorption of the immunosuppressant tacrolimus.

Methods: Liquid SME mixture, composed of Cremophor RH40 and monocaprylin glycerate, was blended with polyethylene oxide, chitosan, polyvinylpyrrolidone and mannitol, and then transformed into tablets via granulation, with ethanol as the wetting agent. The tablets were characterized in respect of swelling, bioadhesive and SME properties. In vitro dissolution was conducted using an HCl buffer at pH 1.2. Oral bioavailability of the tablets was examined in fasted beagle dogs.

Results: The tablet could expand to 13.5 mm in diameter and 15 mm in thickness during the initial 20 min of contact with the HCl buffer at pH 1.2. The bioadhesive strength was as high as 0.98±0.06 N/cm(2). The SME gastroretentive sustained-release tablets preserved the SME capability of the liquid SME formations under transmission electron microscope. The drug-release curve was fit to the zero-order release model, which was helpful in reducing fluctuations in blood concentration. Compared with the commercially available capsules of tacrolimus, the relative bioavailability of the SME gastroretentive sustained-release tablets was 553.4%±353.8%.

Conclusion: SME gastroretentive sustained-release tablets can enhance the oral bioavailability of tacrolimus with poor solubility and a narrow absorption window.

Citing Articles

Solid dispersion systems for enhanced dissolution of poorly water-soluble candesartan cilexetil: In vitro evaluation and simulated pharmacokinetics studies.

Ali I, Sajad U, Abdul Rasool B PLoS One. 2024; 19(6):e0303900.

PMID: 38843120 PMC: 11156308. DOI: 10.1371/journal.pone.0303900.

Features and Facts of a Gastroretentive Drug Delivery System-A Review.

Vinchurkar K, Sainy J, Khan M, Mane S, Mishra D, Dixit P Turk J Pharm Sci. 2022; 19(4):476-487.

PMID: 36047602 PMC: 9438753. DOI: 10.4274/tjps.galenos.2021.44959.

Current Status of Supersaturable Self-Emulsifying Drug Delivery Systems.

Park H, Ha E, Kim M Pharmaceutics. 2020; 12(4).

PMID: 32316199 PMC: 7238279. DOI: 10.3390/pharmaceutics12040365.

Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets.

Chi Z, Azhar I, Khan H, Yang L, Feng Y Sci Rep. 2019; 9(1):17114.

PMID: 31745201 PMC: 6863837. DOI: 10.1038/s41598-019-53750-w.

In Vitro and In Vivo Test Methods for the Evaluation of Gastroretentive Dosage Forms.

Schneider F, Koziolek M, Weitschies W Pharmaceutics. 2019; 11(8).

PMID: 31426417 PMC: 6723944. DOI: 10.3390/pharmaceutics11080416.

References

Nazzal S, Nutan M, Palamakula A, Shah R, Zaghloul A, Khan M . Optimization of a self-nanoemulsified tablet dosage form of Ubiquinone using response surface methodology: effect of formulation ingredients. Int J Pharm. 2002; 240(1-2):103-14. DOI: 10.1016/s0378-5173(02)00130-8. View

Gursoy R, Benita S . Self-emulsifying drug delivery systems (SEDDS) for improved oral delivery of lipophilic drugs. Biomed Pharmacother. 2004; 58(3):173-82. DOI: 10.1016/j.biopha.2004.02.001. View

Parikh D, Amin A . In vitro and in vivo techniques to assess the performance of gastro-retentive drug delivery systems: a review. Expert Opin Drug Deliv. 2008; 5(9):951-65. DOI: 10.1517/17425247.5.9.951. View

Tamura S, Ohike A, Ibuki R, Amidon G, Yamashita S . Tacrolimus is a class II low-solubility high-permeability drug: the effect of P-glycoprotein efflux on regional permeability of tacrolimus in rats. J Pharm Sci. 2002; 91(3):719-29. DOI: 10.1002/jps.10041. View

Kim C . Effects of drug solubility, drug loading, and polymer molecular weight on drug release from Polyox tablets. Drug Dev Ind Pharm. 1999; 24(7):645-51. DOI: 10.3109/03639049809082366. View

Tamura S, Tokunaga Y, Ibuki R, Amidon G, Sezaki H, Yamashita S . The site-specific transport and metabolism of tacrolimus in rat small intestine. J Pharmacol Exp Ther. 2003; 306(1):310-6. DOI: 10.1124/jpet.103.050716. View

Tuleu C, Newton M, Rose J, Euler D, Saklatvala R, Clarke A . Comparative bioavailability study in dogs of a self-emulsifying formulation of progesterone presented in a pellet and liquid form compared with an aqueous suspension of progesterone. J Pharm Sci. 2004; 93(6):1495-502. DOI: 10.1002/jps.20068. View

Balakrishnan P, Lee B, Oh D, Kim J, Hong M, Jee J . Enhanced oral bioavailability of dexibuprofen by a novel solid self-emulsifying drug delivery system (SEDDS). Eur J Pharm Biopharm. 2009; 72(3):539-45. DOI: 10.1016/j.ejpb.2009.03.001. View

Wu N, Wang L, Tan D, Moochhala S, Yang Y . Mathematical modeling and in vitro study of controlled drug release via a highly swellable and dissoluble polymer matrix: polyethylene oxide with high molecular weights. J Control Release. 2005; 102(3):569-81. DOI: 10.1016/j.jconrel.2004.11.002. View

10.

Yamashita K, Nakate T, Okimoto K, Ohike A, Tokunaga Y, Ibuki R . Establishment of new preparation method for solid dispersion formulation of tacrolimus. Int J Pharm. 2003; 267(1-2):79-91. DOI: 10.1016/j.ijpharm.2003.07.010. View

11.

Strubing S, Abboud T, Contri R, Metz H, Mader K . New insights on poly(vinyl acetate)-based coated floating tablets: characterisation of hydration and CO2 generation by benchtop MRI and its relation to drug release and floating strength. Eur J Pharm Biopharm. 2008; 69(2):708-17. DOI: 10.1016/j.ejpb.2007.12.009. View

12.

Tang B, Cheng G, Gu J, Xu C . Development of solid self-emulsifying drug delivery systems: preparation techniques and dosage forms. Drug Discov Today. 2008; 13(13-14):606-12. DOI: 10.1016/j.drudis.2008.04.006. View

13.

Kino T, Hatanaka H, Hashimoto M, Nishiyama M, Goto T, OKUHARA M . FK-506, a novel immunosuppressant isolated from a Streptomyces. I. Fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1987; 40(9):1249-55. DOI: 10.7164/antibiotics.40.1249. View

14.

Streubel A, Siepmann J, Bodmeier R . Gastroretentive drug delivery systems. Expert Opin Drug Deliv. 2006; 3(2):217-33. DOI: 10.1517/17425247.3.2.217. View

15.

Li H, Hardy R, Gu X . Effect of drug solubility on polymer hydration and drug dissolution from polyethylene oxide (PEO) matrix tablets. AAPS PharmSciTech. 2008; 9(2):437-43. PMC: 2976924. DOI: 10.1208/s12249-008-9060-x. View

16.

Venkataramanan R, Swaminathan A, Prasad T, Jain A, Zuckerman S, Warty V . Clinical pharmacokinetics of tacrolimus. Clin Pharmacokinet. 1995; 29(6):404-30. DOI: 10.2165/00003088-199529060-00003. View

17.

Kagayama A, Tanimoto S, Fujisaki J, Kaibara A, Ohara K, Iwasaki K . Oral absorption of FK506 in rats. Pharm Res. 1993; 10(10):1446-50. DOI: 10.1023/a:1018967107612. View

18.

Nazzal S, Khan M . Controlled release of a self-emulsifying formulation from a tablet dosage form: stability assessment and optimization of some processing parameters. Int J Pharm. 2006; 315(1-2):110-21. DOI: 10.1016/j.ijpharm.2006.02.019. View

19.

Serratoni M, Newton M, Booth S, Clarke A . Controlled drug release from pellets containing water-insoluble drugs dissolved in a self-emulsifying system. Eur J Pharm Biopharm. 2006; 65(1):94-8. DOI: 10.1016/j.ejpb.2006.07.011. View

20.

Constantinides P . Lipid microemulsions for improving drug dissolution and oral absorption: physical and biopharmaceutical aspects. Pharm Res. 1995; 12(11):1561-72. DOI: 10.1023/a:1016268311867. View