Effect of Stabilizer on the Maximum Degree and Extent of Supersaturation and Oral Absorption of Tacrolimus Made by Ultra-rapid Freezing

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2007 Oct 31

PMID 17968635

Citations 15

Authors

Kirk A Overhoff

Jason T McConville

Wei Yang

Keith P Johnston

Jay I Peters

Robert O Williams 3rd

Affiliations

Soon will be listed here.

Abstract

Purpose: Solid dispersions containing various stabilizers and tacrolimus (TAC) prepared by an Ultra-rapid Freezing (URF) process were investigated to determine the effect on their ability to form supersaturated solutions in aqueous media and on enhancing transport across biological membranes.

Materials And Methods: The stabilizers included poly(vinyl alcohol; PVA), poloxamer 407 (P407), and sodium dodecyl sulfate (SDS). In vivo absorption enhancement in rats was also investigated. Dissolution studies were conducted at supersaturated conditions in both acidic media for 24 h and at delayed release (enteric) conditions to simulate intestinal transit.

Results: The rank order of C/Ceq(max) in the dissolution studies at acidic conditions was URF-P407 > URF-SDS > Prograf (PRO) > URF-PVA:P407. For C/Ceq(max) under enteric conditions, the order was URF-SDS > PRO > URF-PVA:P407 > URF-P407, and for the extent of supersaturation (AUC) in acidic and pH shift conditions it was URF-SDS>PRO>URF-PVA:P407>URF-P407. The pharmacokinetic data suggests URF-P407 had the greatest absorption having higher C (max) with a 1.5-fold increase in AUC compared to PRO. All URF compositions had a shorter T (max) compared to PRO.

Conclusions: The nanostructured powders containing various stabilizing polymers formed by the URF process offer enhanced supersaturation characteristics leading to increased oral absorption of TAC.

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References

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

Gao P, Guyton M, Huang T, Bauer J, Stefanski K, Lu Q . Enhanced oral bioavailability of a poorly water soluble drug PNU-91325 by supersaturatable formulations. Drug Dev Ind Pharm. 2004; 30(2):221-9. DOI: 10.1081/ddc-120028718. View

McConville J, Overhoff K, Sinswat P, Vaughn J, Frei B, Burgess D . Targeted high lung concentrations of itraconazole using nebulized dispersions in a murine model. Pharm Res. 2006; 23(5):901-11. DOI: 10.1007/s11095-006-9904-6. View

Raghavan S, Trividic A, Davis A, Hadgraft J . Crystallization of hydrocortisone acetate: influence of polymers. Int J Pharm. 2001; 212(2):213-21. DOI: 10.1016/s0378-5173(00)00610-4. View

Raghavan S, Trividic A, Davis A, Hadgraft J . Effect of cellulose polymers on supersaturation and in vitro membrane transport of hydrocortisone acetate. Int J Pharm. 1999; 193(2):231-7. DOI: 10.1016/s0378-5173(99)00345-2. View

Chutimaworapan S, Ritthidej G, Yonemochi E, Oguchi T, Yamamoto K . Effect of water-soluble carriers on dissolution characteristics of nifedipine solid dispersions. Drug Dev Ind Pharm. 2000; 26(11):1141-50. DOI: 10.1081/ddc-100100985. View

Lee M, Straubinger R, Jusko W . Physicochemical, pharmacokinetic and pharmacodynamic evaluation of liposomal tacrolimus (FK 506) in rats. Pharm Res. 1995; 12(7):1055-9. DOI: 10.1023/a:1016222817860. View

Chiou W, Chung S, Wu T . Apparent lack of effect of P-glycoprotein on the gastrointestinal absorption of a substrate, tacrolimus, in normal mice. Pharm Res. 2000; 17(2):205-8. DOI: 10.1023/a:1007573531947. View

Vaughn J, McConville J, Crisp M, Johnston K, Williams 3rd R . Supersaturation produces high bioavailability of amorphous danazol particles formed by evaporative precipitation into aqueous solution and spray freezing into liquid technologies. Drug Dev Ind Pharm. 2006; 32(5):559-67. DOI: 10.1080/03639040500529176. View

10.

Arima H, Yunomae K, Hirayama F, Uekama K . Contribution of P-glycoprotein to the enhancing effects of dimethyl-beta-cyclodextrin on oral bioavailability of tacrolimus. J Pharmacol Exp Ther. 2001; 297(2):547-55. View

11.

Arima H, Yunomae K, Miyake K, Irie T, Hirayama F, Uekama K . Comparative studies of the enhancing effects of cyclodextrins on the solubility and oral bioavailability of tacrolimus in rats. J Pharm Sci. 2001; 90(6):690-701. DOI: 10.1002/jps.1025. View

12.

Mancinelli L, Frassetto L, Floren L, Dressler D, Carrier S, BEKERSKY I . The pharmacokinetics and metabolic disposition of tacrolimus: a comparison across ethnic groups. Clin Pharmacol Ther. 2001; 69(1):24-31. DOI: 10.1067/mcp.2001.113183. View

13.

Overhoff K, Engstrom J, Chen B, Scherzer B, Milner T, Johnston K . Novel ultra-rapid freezing particle engineering process for enhancement of dissolution rates of poorly water-soluble drugs. Eur J Pharm Biopharm. 2006; 65(1):57-67. DOI: 10.1016/j.ejpb.2006.07.012. View

14.

Nishikawa T, Hasumi H, Suzuki S, Kubo H, Ohtani H . Kinetic analysis of molecular interconversion of immunosuppressant FK506 by high-performance liquid chromatography. Pharm Res. 1993; 10(12):1785-9. DOI: 10.1023/a:1018938618032. View

15.

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

16.

Raghavan S, Kiepfer B, Davis A, Kazarian S, Hadgraft J . Membrane transport of hydrocortisone acetate from supersaturated solutions; the role of polymers. Int J Pharm. 2001; 221(1-2):95-105. DOI: 10.1016/s0378-5173(01)00673-1. View

17.

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

18.

Imaizumi H, Nambu N, Nagai T . Stability and several physical properties of amorphous and crystalline form of indomethacin. Chem Pharm Bull (Tokyo). 1980; 28(9):2565-9. DOI: 10.1248/cpb.28.2565. View

19.

Vaughn J, McConville J, Burgess D, Peters J, Johnston K, Talbert R . Single dose and multiple dose studies of itraconazole nanoparticles. Eur J Pharm Biopharm. 2006; 63(2):95-102. DOI: 10.1016/j.ejpb.2006.01.006. View

20.

Suzuki H, Sunada H . Influence of water-soluble polymers on the dissolution of nifedipine solid dispersions with combined carriers. Chem Pharm Bull (Tokyo). 1998; 46(3):482-7. DOI: 10.1248/cpb.46.482. View