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Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF.
AAPS PharmSciTech. 2015 Aug; 16(4):824-34.AP

Abstract

The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes.

Authors+Show Affiliations

Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

25567525

Citation

Alshahrani, Saad M., et al. "Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions Via Combinations of Soluplus® and HPMCAS-HF." AAPS PharmSciTech, vol. 16, no. 4, 2015, pp. 824-34.
Alshahrani SM, Lu W, Park JB, et al. Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech. 2015;16(4):824-34.
Alshahrani, S. M., Lu, W., Park, J. B., Morott, J. T., Alsulays, B. B., Majumdar, S., Langley, N., Kolter, K., Gryczke, A., & Repka, M. A. (2015). Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech, 16(4), 824-34. https://doi.org/10.1208/s12249-014-0269-6
Alshahrani SM, et al. Stability-enhanced Hot-melt Extruded Amorphous Solid Dispersions Via Combinations of Soluplus® and HPMCAS-HF. AAPS PharmSciTech. 2015;16(4):824-34. PubMed PMID: 25567525.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Stability-enhanced hot-melt extruded amorphous solid dispersions via combinations of Soluplus® and HPMCAS-HF. AU - Alshahrani,Saad M, AU - Lu,Wenli, AU - Park,Jun-Bom, AU - Morott,Joseph T, AU - Alsulays,Bader B, AU - Majumdar,Soumyajit, AU - Langley,Nigel, AU - Kolter,Karl, AU - Gryczke,Andreas, AU - Repka,Michael A, Y1 - 2015/01/08/ PY - 2014/09/30/received PY - 2014/12/08/accepted PY - 2015/1/9/entrez PY - 2015/1/9/pubmed PY - 2016/4/16/medline SP - 824 EP - 34 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 16 IS - 4 N2 - The aim of this study was to evaluate a novel combination of Soluplus® and hypromellose acetate succinate (HPMCAS-HF) polymers for solubility enhancement as well as enhanced physicochemical stability of the produced amorphous solid dispersions. This was accomplished by converting the poorly water-soluble crystalline form of carbamazepine into a more soluble amorphous form within the polymeric blends. Carbamazepine (CBZ), a Biopharmaceutics Classification System class II active pharmaceutical ingredient (API) with multiple polymorphs, was utilized as a model drug. Hot-melt extrusion (HME) processing was used to prepare solid dispersions utilizing blends of polymers. Drug loading showed a significant effect on the dissolution rate of CBZ in all of the tested ratios of Soluplus® and HPMCAS-HF. CBZ was completely miscible in the polymeric blends of Soluplus® and HPMCAS-HF up to 40% drug loading. The extrudates were characterized by differential scanning calorimetry (DSC), X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy and dissolution studies. DSC and XRD data confirmed the formation of amorphous solid dispersions of CBZ in the polymeric blends of Soluplus® and HPMCAS-HF. Drug loading and release of CBZ was increased with Soluplus® (when used as the primary matrix polymer) when formulations contained Soluplus® with 7-21% (w/w) HPMCAS-HF. In addition, this blend of polymers was found to be physically and chemically stable at 40°C, 75% RH over 12 months without any dissolution rate changes. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/25567525/Stability_enhanced_hot_melt_extruded_amorphous_solid_dispersions_via_combinations_of_Soluplus®_and_HPMCAS_HF_ L2 - https://dx.doi.org/10.1208/s12249-014-0269-6 DB - PRIME DP - Unbound Medicine ER -