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Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound.
AAPS PharmSciTech. 2017 Nov; 18(8):3140-3150.AP

Abstract

The purpose of this research was to design and characterize an immediate-release formulation of carbamazepine (CBZ), a poorly soluble anti-epileptic drug, using a porous silica carrier. Carbon dioxide in its supercritical state (2000 psi, 30-35°C) was used as an anti-solvent to precipitate CBZ onto two particle size variants of silica. Adsorption isotherms were used as a pre-formulation strategy to select optimum ratios of silica and CBZ. The obtained drug-silica formulations were characterized by dissolution studies, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). This formulation strategy resulted in a 2.4-fold improvement in dissolution rate when compared to pure drug after 30 min of dissolution testing. PXRD and DSC confirmed the amorphous nature of CBZ in the formulations as well as the differences in polymorphic forms of commercial and supercritical fluid-processed CBZ. Additionally, solid-state NMR spectroscopy showed that the spin-lattice relaxation time for bulk drug (without silica) was ∼7.5 times greater than that for silica-confined CBZ, implying that when CBZ was adsorbed onto mesoporous silica, it is structurally disordered and had higher structural mobility, a characteristic of amorphous solids. The mesoporous silica matrix prevented CBZ crystal growth by imposing spatial constraint on CBZ nuclei and hence resulted in faster dissolution compared to bulk solid drug. Adsorption onto mesoporous silica using supercritical fluid technology may be used as a novel formulation strategy for amorphization of poorly soluble compounds, in turn improving their dissolution rate.

Authors+Show Affiliations

Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, USA. adityavgandhi88@gmail.com. Department of Pharmaceutical Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA. adityavgandhi88@gmail.com.Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, USA.Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, USA.Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, Queens, New York, USA.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28534299

Citation

Gandhi, Aditya V., et al. "Adsorption Onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound." AAPS PharmSciTech, vol. 18, no. 8, 2017, pp. 3140-3150.
Gandhi AV, Thipsay P, Kirthivasan B, et al. Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound. AAPS PharmSciTech. 2017;18(8):3140-3150.
Gandhi, A. V., Thipsay, P., Kirthivasan, B., & Squillante, E. (2017). Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound. AAPS PharmSciTech, 18(8), 3140-3150. https://doi.org/10.1208/s12249-017-0784-3
Gandhi AV, et al. Adsorption Onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound. AAPS PharmSciTech. 2017;18(8):3140-3150. PubMed PMID: 28534299.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Adsorption onto Mesoporous Silica Using Supercritical Fluid Technology Improves Dissolution Rate of Carbamazepine-a Poorly Soluble Compound. AU - Gandhi,Aditya V, AU - Thipsay,Priyanka, AU - Kirthivasan,Bharat, AU - Squillante,Emilio, Y1 - 2017/05/22/ PY - 2017/02/02/received PY - 2017/04/13/accepted PY - 2017/5/24/pubmed PY - 2018/5/10/medline PY - 2017/5/24/entrez KW - amorphous KW - dissolution rate KW - mesoporous silica KW - solid-state NMR KW - supercritical fluid technology SP - 3140 EP - 3150 JF - AAPS PharmSciTech JO - AAPS PharmSciTech VL - 18 IS - 8 N2 - The purpose of this research was to design and characterize an immediate-release formulation of carbamazepine (CBZ), a poorly soluble anti-epileptic drug, using a porous silica carrier. Carbon dioxide in its supercritical state (2000 psi, 30-35°C) was used as an anti-solvent to precipitate CBZ onto two particle size variants of silica. Adsorption isotherms were used as a pre-formulation strategy to select optimum ratios of silica and CBZ. The obtained drug-silica formulations were characterized by dissolution studies, differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), and scanning electron microscopy (SEM). This formulation strategy resulted in a 2.4-fold improvement in dissolution rate when compared to pure drug after 30 min of dissolution testing. PXRD and DSC confirmed the amorphous nature of CBZ in the formulations as well as the differences in polymorphic forms of commercial and supercritical fluid-processed CBZ. Additionally, solid-state NMR spectroscopy showed that the spin-lattice relaxation time for bulk drug (without silica) was ∼7.5 times greater than that for silica-confined CBZ, implying that when CBZ was adsorbed onto mesoporous silica, it is structurally disordered and had higher structural mobility, a characteristic of amorphous solids. The mesoporous silica matrix prevented CBZ crystal growth by imposing spatial constraint on CBZ nuclei and hence resulted in faster dissolution compared to bulk solid drug. Adsorption onto mesoporous silica using supercritical fluid technology may be used as a novel formulation strategy for amorphization of poorly soluble compounds, in turn improving their dissolution rate. SN - 1530-9932 UR - https://www.unboundmedicine.com/medline/citation/28534299/Adsorption_onto_Mesoporous_Silica_Using_Supercritical_Fluid_Technology_Improves_Dissolution_Rate_of_Carbamazepine_a_Poorly_Soluble_Compound_ L2 - https://dx.doi.org/10.1208/s12249-017-0784-3 DB - PRIME DP - Unbound Medicine ER -