Molecular Weight Effects on the Miscibility Behavior of Dextran and Maltodextrin with Poly(vinylpyrrolidone)

Overview

Journal Pharm Res

Specialties Pharmacology
Pharmacy

Date 2012 Feb 3

PMID 22297824

Authors

Bernard Van Eerdenbrugh

Lynne S Taylor

Affiliations

Soon will be listed here.

Abstract

Purpose: To characterize and interpret the miscibility of dextran and maltodextrin with poly(vinylpyrrolidone) (DEX-PVP) as a function of polymer molecular weights.

Methods: Blend miscibility was studied using 4 different molecular weight (MW) grades of DEX combined with 5 MW grades of PVP, over a broad compositional range. Miscibility was evaluated by inspection of glass transition events measured by differential scanning calorimetry (DSC). Fourier transform mid-infrared spectroscopy (FTIR), combined with curve fitting, was performed to characterize the extent of hydrogen bonding. The observed miscibility behavior was further interpreted in terms of mixing thermodynamics.

Results: Miscibility of the blends ranged from fully miscible to completely immiscible with multiple partially miscible systems observed. Increasing polymer molecular weight decreased miscibility. For the lowest DEX grade, hydrogen bonding was independent of PVP MW, as expected since all systems were completely miscible. Higher molecular weights of DEX resulted in reduced intermolecular hydrogen bonding and decreased miscibility, increasingly so for higher MW PVP grades. Evaluation of the mixing thermodynamics supported these findings.

Conclusions: With higher combined molecular weights of DEX-PVP blends, phase behavior evolves from completely miscible to virtually immiscible. Concurrently, DEX-PVP hydrogen bonding decreases. From a thermodynamic perspective, the combinatorial mixing entropy was observed to decrease as the molecular weight of the polymers increased, providing a reduced counterbalance to the unfavorable mixing enthalpy thought to accompany this polymer combination.

References

Van Eerdenbrugh B, Taylor L . Small scale screening to determine the ability of different polymers to inhibit drug crystallization upon rapid solvent evaporation. Mol Pharm. 2010; 7(4):1328-37. DOI: 10.1021/mp1001153. View

Qi S, Belton P, Nollenberger K, Clayden N, Reading M, Craig D . Characterisation and prediction of phase separation in hot-melt extruded solid dispersions: a thermal, microscopic and NMR relaxometry study. Pharm Res. 2010; 27(9):1869-83. DOI: 10.1007/s11095-010-0185-8. View

Baird J, Taylor L . Evaluation of amorphous solid dispersion properties using thermal analysis techniques. Adv Drug Deliv Rev. 2011; 64(5):396-421. DOI: 10.1016/j.addr.2011.07.009. View

Rumondor A, Ivanisevic I, Bates S, Alonzo D, Taylor L . Evaluation of drug-polymer miscibility in amorphous solid dispersion systems. Pharm Res. 2009; 26(11):2523-34. DOI: 10.1007/s11095-009-9970-7. View

Izutsu K, Aoyagi N, Kojima S . Effect of polymer size and cosolutes on phase separation of poly(vinylpyrrolidone) (PVP) and dextran in frozen solutions. J Pharm Sci. 2005; 94(4):709-17. DOI: 10.1002/jps.20292. View

Pham T, Watson S, Edwards A, Chavda M, Clawson J, Strohmeier M . Analysis of amorphous solid dispersions using 2D solid-state NMR and (1)H T(1) relaxation measurements. Mol Pharm. 2010; 7(5):1667-91. DOI: 10.1021/mp100205g. View

Zhang J, Bunker M, Parker A, Madden-Smith C, Patel N, Roberts C . The stability of solid dispersions of felodipine in polyvinylpyrrolidone characterized by nanothermal analysis. Int J Pharm. 2011; 414(1-2):210-7. DOI: 10.1016/j.ijpharm.2011.05.037. View

Lauer M, Grassmann O, Siam M, Tardio J, Jacob L, Page S . Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharm Res. 2010; 28(3):572-84. PMC: 3044090. DOI: 10.1007/s11095-010-0306-4. View

Izutsu K, Fujii K, Katori C, Yomota C, Kawanishi T, Yoshihashi Y . Effects of solute miscibility on the micro- and macroscopic structural integrity of freeze-dried solids. J Pharm Sci. 2010; 99(11):4710-9. DOI: 10.1002/jps.22170. View

10.

Aso Y, Yoshioka S, Miyazaki T, Kawanishi T, Tanaka K, Kitamura S . Miscibility of nifedipine and hydrophilic polymers as measured by (1)H-NMR spin-lattice relaxation. Chem Pharm Bull (Tokyo). 2007; 55(8):1227-31. DOI: 10.1248/cpb.55.1227. View

11.

Rumondor A, Marsac P, Stanford L, Taylor L . Phase behavior of poly(vinylpyrrolidone) containing amorphous solid dispersions in the presence of moisture. Mol Pharm. 2009; 6(5):1492-505. DOI: 10.1021/mp900050c. View

12.

Padilla A, Pikal M . The study of phase separation in amorphous freeze-dried systems, part 2: investigation of Raman mapping as a tool for studying amorphous phase separation in freeze-dried protein formulations. J Pharm Sci. 2010; 100(4):1467-74. DOI: 10.1002/jps.22380. View

13.

Newman A, Engers D, Bates S, Ivanisevic I, Kelly R, Zografi G . Characterization of amorphous API:Polymer mixtures using X-ray powder diffraction. J Pharm Sci. 2008; 97(11):4840-56. DOI: 10.1002/jps.21352. View

14.

Qi S, Belton P, Nollenberger K, Gryczke A, Craig D . Compositional analysis of low quantities of phase separation in hot-melt-extruded solid dispersions: a combined atomic force microscopy, photothermal fourier-transform infrared microspectroscopy, and localised thermal analysis approach. Pharm Res. 2011; 28(9):2311-26. DOI: 10.1007/s11095-011-0461-2. View

15.

Shamblin S, TAYLOR L, Zografi G . Mixing behavior of colyophilized binary systems. J Pharm Sci. 1998; 87(6):694-701. DOI: 10.1021/js9704801. View

16.

Padilla A, Chou S, Luthra S, Pikal M . The study of amorphous phase separation in a model polymer phase-separating system using Raman microscopy and a low-temperature stage: effect of cooling rate and nucleation temperature. J Pharm Sci. 2010; 100(4):1362-76. DOI: 10.1002/jps.22357. 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.

Six K, Murphy J, Weuts I, Craig D, Verreck G, Peeters J . Identification of phase separation in solid dispersions of itraconazole and Eudragit E100 using microthermal analysis. Pharm Res. 2003; 20(1):135-8. DOI: 10.1023/a:1022219429708. View

19.

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

20.

Van Eerdenbrugh B, Taylor L . Application of mid-IR spectroscopy for the characterization of pharmaceutical systems. Int J Pharm. 2010; 417(1-2):3-16. DOI: 10.1016/j.ijpharm.2010.12.011. View