Effects of Polymer Type and Storage Relative Humidity on the Kinetics of Felodipine Crystallization from Amorphous Solid Dispersions

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2009 Oct 7

PMID 19806435

Citations 33

Authors

Alfred C F Rumondor

Lindsay A Stanford

Lynne S Taylor

Affiliations

Soon will be listed here.

Abstract

Purpose: The objective of this study was to investigate the effects of polymer type and storage relative humidity (RH) on the crystallization kinetics of felodipine from amorphous solid dispersions.

Methods: Crystallization of the model drug felodipine from amorphous solid dispersion samples containing poly(vinyl pyrrolidone) (PVP) and hypromellose acetate succinate (HPMCAS) were evaluated. Samples at three different drug-polymer weight ratios (10, 25, and 50 wt. % polymer) were prepared and stored at six different RHs (0%, 32%, 52% or 66%, 75%, 86%, and 93%). Periodically, the fraction of the drug that had crystallized from the samples was quantified using powder X-ray diffractometry (PXRD).

Results: Felodipine crystallization rates from PVP-containing dispersions were found to be very sensitive to changes in storage RH, while crystallization rates from HPMCAS-containing dispersions were not. PVP and HPMCAS were similar in terms of their ability to inhibit crystallization at low RH, but when the storage RH was increased to 75% or above, felodipine crystallization from PVP-containing solid dispersions proceeded much faster. It is hypothesized that this trend was caused by moisture-induced drug-polymer immiscibility in PVP-felodipine system. For PVP-containing solid dispersion samples stored at 75% RH and above, crystallization of the model drug felodipine seemed to approach a kinetic plateau, whereby a fraction of the drug still remained amorphous even after storage for 500 days or more.

Conclusions: The physical stability of solid dispersions as a function of RH is highly dependent on the polymer used to form the solid dispersion, with PVP-containing dispersions being much less physically stable at high RH than HPMCAS-containing dispersions.

Citing Articles

Kinetic and Thermodynamic Interplay of Polymer-Mediated Liquid-Liquid Phase Separation for Poorly Water-Soluble Drugs.

Qian K, Stella L, Liu F, Jones D, Andrews G, Tian Y Mol Pharm. 2024; 21(6):2878-2893.

PMID: 38767457 PMC: 11151203. DOI: 10.1021/acs.molpharmaceut.4c00033.

Emerging Applications of Hydroxypropyl Methylcellulose Acetate Succinate: Different Aspects in Drug Delivery and Its Commercial Potential.

Choudhari M, Damle S, Saha R, Dubey S, Singhvi G AAPS PharmSciTech. 2023; 24(7):188.

PMID: 37715004 DOI: 10.1208/s12249-023-02645-1.

Exploring molecular reorientations in amorphous and recrystallized felodipine at the microscopic level.

Pajzderska A, Jenczyk J, Embs J, Wasicki J RSC Adv. 2022; 10(61):37346-37357.

PMID: 35521258 PMC: 9057141. DOI: 10.1039/d0ra07266d.

The Physical Stability of Felodipine and Its Recrystallization from an Amorphous Solid Dispersion Studied by NMR Relaxometry.

Pajzderska A, Mielcarek J, Wasicki J AAPS PharmSciTech. 2022; 23(4):93.

PMID: 35314906 DOI: 10.1208/s12249-022-02234-8.

Influence of Storage Conditions on the Stability of Gum Arabic and Tragacanth.

Ramos P, Broncel M Molecules. 2022; 27(5).

PMID: 35268614 PMC: 8911758. DOI: 10.3390/molecules27051510.

References

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

Konno H, Taylor L . Ability of different polymers to inhibit the crystallization of amorphous felodipine in the presence of moisture. Pharm Res. 2007; 25(4):969-78. DOI: 10.1007/s11095-007-9331-3. View

Andronis V, Yoshioka M, Zografi G . Effects of sorbed water on the crystallization of indomethacin from the amorphous state. J Pharm Sci. 1997; 86(3):346-51. DOI: 10.1021/js9602711. View

Aso Y, Yoshioka S . Molecular mobility of nifedipine-PVP and phenobarbital-PVP solid dispersions as measured by 13C-NMR spin-lattice relaxation time. J Pharm Sci. 2005; 95(2):318-25. DOI: 10.1002/jps.20545. View

Konno H, Taylor L . Influence of different polymers on the crystallization tendency of molecularly dispersed amorphous felodipine. J Pharm Sci. 2006; 95(12):2692-705. DOI: 10.1002/jps.20697. 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

van den Mooter G, Wuyts M, Blaton N, Busson R, Grobet P, Augustijns P . Physical stabilisation of amorphous ketoconazole in solid dispersions with polyvinylpyrrolidone K25. Eur J Pharm Sci. 2000; 12(3):261-9. DOI: 10.1016/s0928-0987(00)00173-1. View

Marsac P, Konno H, Taylor L . A comparison of the physical stability of amorphous felodipine and nifedipine systems. Pharm Res. 2006; 23(10):2306-16. DOI: 10.1007/s11095-006-9047-9. View

Shamblin S, Zografi G . The effects of absorbed water on the properties of amorphous mixtures containing sucrose. Pharm Res. 1999; 16(7):1119-24. DOI: 10.1023/a:1018960405504. View

10.

Zhou D, Zhang G, Law D, Grant D, Schmitt E . Physical stability of amorphous pharmaceuticals: Importance of configurational thermodynamic quantities and molecular mobility. J Pharm Sci. 2002; 91(8):1863-72. DOI: 10.1002/jps.10169. View

11.

Shah B, Kakumanu V, Bansal A . Analytical techniques for quantification of amorphous/crystalline phases in pharmaceutical solids. J Pharm Sci. 2006; 95(8):1641-65. DOI: 10.1002/jps.20644. View

12.

Verreck G, Six K, Van den Mooter G, Baert L, Peeters J, Brewster M . Characterization of solid dispersions of itraconazole and hydroxypropylmethylcellulose prepared by melt extrusion--Part I. Int J Pharm. 2003; 251(1-2):165-74. DOI: 10.1016/s0378-5173(02)00591-4. View

13.

Ford J . The current status of solid dispersions. Pharm Acta Helv. 1986; 61(3):69-88. View

14.

Miyazaki T, Yoshioka S, Aso Y . Physical stability of amorphous acetanilide derivatives improved by polymer excipients. Chem Pharm Bull (Tokyo). 2006; 54(8):1207-10. DOI: 10.1248/cpb.54.1207. View

15.

Rollinger J, Burger A . Polymorphism of racemic felodipine and the unusual series of solid solutions in the binary system of its enantiomers. J Pharm Sci. 2001; 90(7):949-59. DOI: 10.1002/jps.1046. View

16.

Miyazaki T, Yoshioka S, Aso Y, Kojima S . Ability of polyvinylpyrrolidone and polyacrylic acid to inhibit the crystallization of amorphous acetaminophen. J Pharm Sci. 2004; 93(11):2710-7. DOI: 10.1002/jps.20182. View

17.

Marsac P, Rumondor A, Nivens D, Kestur U, Stanciu L, Taylor L . Effect of temperature and moisture on the miscibility of amorphous dispersions of felodipine and poly(vinyl pyrrolidone). J Pharm Sci. 2009; 99(1):169-85. DOI: 10.1002/jps.21809. View

18.

Khougaz K, Clas S . Crystallization inhibition in solid dispersions of MK-0591 and poly(vinylpyrrolidone) polymers. J Pharm Sci. 2000; 89(10):1325-34. DOI: 10.1002/1520-6017(200010)89:10<1325::aid-jps10>3.0.co;2-5. View

19.

Matsumoto T, Zografi G . Physical properties of solid molecular dispersions of indomethacin with poly(vinylpyrrolidone) and poly(vinylpyrrolidone-co-vinyl-acetate) in relation to indomethacin crystallization. Pharm Res. 1999; 16(11):1722-8. DOI: 10.1023/a:1018906132279. View

20.

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