Utility of Hydroxypropylmethylcellulose Acetate Succinate (HPMCAS) for Initiation and Maintenance of Drug Supersaturation in the GI Milieu

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2009 Mar 12

PMID 19277850

Citations 55

Authors

William Curatolo

James A Nightingale

Scott M Herbig

Affiliations

Soon will be listed here.

Abstract

Purpose: To identify materials and processes which effect supersaturation of the GI milieu for low solubility drugs in order to increase oral bioavailability.

Methods: A variety of small and polymeric molecules were screened for their ability to inhibit drug precipitation in supersaturated solutions. The best polymeric materials were utilized to create spray-dried dispersions (SDDs) of drug and polymer, and these were tested for drug form and homogeneity. Dispersions were tested in vitro for their ability to achieve and maintain drug supersaturation, for a variety of drug structures.

Results: Of the 41 materials tested, HPMCAS was the most effective at maintaining drug supersaturation. Drug/HPMCAS SDDs were consistently more effective at achieving and maintaining drug supersaturation in vitro than were SDDs prepared with other polymers. Drug/HPMCAS SDDs were effective in vitro for eight low solubility drugs of widely varying structure. Drug/HPMCAS SDDs were more effective at achieving and maintaining supersaturation than were rotoevaporated Drug/HPMCAS dispersions or physical mixtures of Drug and HPMCAS. The degree of achievable drug supersaturation increased with increasing polymer content in the SDD. The drug in Drug /HPMCAS SDDs was amorphous, and the dispersions were demonstrated to have a single glass transition and were thus homogeneous.

Conclusion: HPMCAS has been identified as a uniquely effective polymer for use in SDDs of low solubility drugs, with broad applicability across a variety of drug structures and properties.

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References

Hernell O, Staggers J, Carey M . Physical-chemical behavior of dietary and biliary lipids during intestinal digestion and absorption. 2. Phase analysis and aggregation states of luminal lipids during duodenal fat digestion in healthy adult human beings. Biochemistry. 1990; 29(8):2041-56. DOI: 10.1021/bi00460a012. View

Chiou W, RIEGELMAN S . Pharmaceutical applications of solid dispersion systems. J Pharm Sci. 1971; 60(9):1281-302. DOI: 10.1002/jps.2600600902. View

Pouton C, Porter C . Formulation of lipid-based delivery systems for oral administration: materials, methods and strategies. Adv Drug Deliv Rev. 2007; 60(6):625-37. DOI: 10.1016/j.addr.2007.10.010. View

Chiou W, RIEGELMAN S . Preparation and dissolution characteristics of several fast-release solid dispersions of griseofulvin. J Pharm Sci. 1969; 58(12):1505-10. DOI: 10.1002/jps.2600581218. View

Serajuddin A . Solid dispersion of poorly water-soluble drugs: early promises, subsequent problems, and recent breakthroughs. J Pharm Sci. 1999; 88(10):1058-66. DOI: 10.1021/js980403l. View

Lipinski C, Lombardo F, Dominy B, Feeney P . Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev. 2001; 46(1-3):3-26. DOI: 10.1016/s0169-409x(00)00129-0. View

Leuner C, Dressman J . Improving drug solubility for oral delivery using solid dispersions. Eur J Pharm Biopharm. 2000; 50(1):47-60. DOI: 10.1016/s0939-6411(00)00076-x. View

Goldberg A, Gibaldi M, KANIG J . Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures. I. Theoretical considerations and discussion of the literature. J Pharm Sci. 1965; 54(8):1145-8. DOI: 10.1002/jps.2600540810. View

Jantratid E, Janssen N, Reppas C, Dressman J . Dissolution media simulating conditions in the proximal human gastrointestinal tract: an update. Pharm Res. 2008; 25(7):1663-76. DOI: 10.1007/s11095-008-9569-4. View

10.

Stoll R, Bates T, Swarbrick J . In vitro dissolution and in vivo absorption of nitrofurantoin from deoxycholic acid coprecipitates. J Pharm Sci. 1973; 62(1):65-8. DOI: 10.1002/jps.2600620111. View

11.

Goldberg A, Gibaldi M, KANIG J, Mayersohn M . Increasing dissolution rates and gastrointestinal absorption of drugs via solid solutions and eutectic mixtures. IV. Chloramphenicol--urea system. J Pharm Sci. 1966; 55(6):581-3. DOI: 10.1002/jps.2600550610. View

12.

Nicolaides E, Symillides M, Dressman J, Reppas C . Biorelevant dissolution testing to predict the plasma profile of lipophilic drugs after oral administration. Pharm Res. 2001; 18(3):380-8. DOI: 10.1023/a:1011071401306. View

13.

Northfield T, McColl I . Postprandial concentrations of free and conjugated bile acids down the length of the normal human small intestine. Gut. 1973; 14(7):513-8. PMC: 1412809. DOI: 10.1136/gut.14.7.513. View

14.

Johnson K, Swindell A . Guidance in the setting of drug particle size specifications to minimize variability in absorption. Pharm Res. 1996; 13(12):1795-8. DOI: 10.1023/a:1016068705255. View

15.

Chiou W, RIEGELMAN S . Oral absorption of griseofulvin in dogs: increased absorption via solid dispersion in polyethylene glycol 6000. J Pharm Sci. 1970; 59(7):937-42. DOI: 10.1002/jps.2600590703. View

16.

Stoll R, Bates T, NIEFORTH K, Swarbrick J . Some physical factors affecting the enhanced blepharoptotic activity of orally administered reserpine-cholanic acid coprecipitates. J Pharm Sci. 1969; 58(12):1457-9. DOI: 10.1002/jps.2600581206. View

17.

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

18.

Horter D, Dressman J . Influence of physicochemical properties on dissolution of drugs in the gastrointestinal tract. Adv Drug Deliv Rev. 2001; 46(1-3):75-87. DOI: 10.1016/s0169-409x(00)00130-7. View

19.

Admirand W, Small D . The physicochemical basis of cholesterol gallstone formation in man. J Clin Invest. 1968; 47(5):1043-52. PMC: 297257. DOI: 10.1172/JCI105794. View

20.

Dokoumetzidis A, Macheras P . A century of dissolution research: from Noyes and Whitney to the biopharmaceutics classification system. Int J Pharm. 2006; 321(1-2):1-11. DOI: 10.1016/j.ijpharm.2006.07.011. View