Enhancement of Aqueous Solubility and Dissolution of Celecoxib through Phosphatidylcholine-Based Dispersion Systems Solidified with Adsorbent Carriers.

Kanghee Jo,Hyunjoo Lee,Jaehwi Lee,Eun Kyung Kim,Jae Min Cho,Hong Chul Kim,Hyeongmin Kim

doi:10.3390/pharmaceutics11010001

Kanghee Jo, Hyunjoo Lee + Show 5 more

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https://doi.org/10.3390/pharmaceutics11010001

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Journal: Pharmaceutics	Publication Date: Dec 20, 2018
Citations: 25	License type: CC BY 4.0

Affiliation: Chung-Ang University

Abstract

This study aimed to design phosphatidylcholine (PC)-based solid dispersion (SD) systems for enhancing the apparent aqueous solubility and dissolution of celecoxib (CLC), a selective cyclooxygenase-2 inhibitor with a highly hydrophobic property. Although PC-based dispersion formulations considerably increased solubilities of CLC, the lipidic texture of PC was not appropriate as a solid dosage form for oral administration of CLC. To mask the lipidic texture of PC-based matrices, Neusilin® US2, an adsorbent material with a porous structure and large surface area widely used in the pharmaceutical industry, was employed and thereby fully powderized PC-based dispersion formulations could be fabricated. However, PC matrices containing CLC strongly adsorbed to the pores of Neusilin® US2 was not able to be rapidly released. To address this problem, different hydrophilic materials were examined to promote the release of the CLC-dispersed PC matrices from Neusilin® US2. Among tested hydrophilic materials, croscarmellose sodium was the most suitable to facilitate fast drug dissolution from Neusilin® US2 particles, showing significantly enhanced apparent aqueous solubility and dissolution behavior of CLC. Through differential scanning calorimetry, X-ray diffraction, and Fourier transform infrared spectroscopy (FT-IR) analysis, a considerably reduced crystallinity of CLC dispersed in the PC-based dispersion formulations was demonstrated. The PC-based SD formulations developed in this study would be useful for improving the oral bioavailability of poorly soluble drugs such as CLC.

Highlights

Celecoxib (CLC) is one of the most commonly prescribed selective cyclooxygenase (COX)-2 inhibitors used for the treatment of acute and chronic pain and inflammation
CLC is classified as Class II drug in accordance with the Biopharmaceutics Classification System (BCS) and the oral bioavailability of CLC is largely governed by its low aqueous solubility of 1.15 μg/mL as measured in our laboratory and slow
Among the various formulations described above, solid dispersion (SD) systems refer to a technique that produces the homogeneous molecular dispersion of hydrophobic drugs in an inert polymeric carrier to alter the crystalline state of the drugs to an amorphous state, which facilitates the fast dissolution of the drugs [5,6,10,11,12,13,14,15,16]

Summary

Introduction

Celecoxib (CLC) is one of the most commonly prescribed selective cyclooxygenase (COX)-2 inhibitors used for the treatment of acute and chronic pain and inflammation. Compared to non-selective non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit COX-1 and COX-2, COX-2 inhibitors such as CLC have been known to cause fewer side effects such as upper gastrointestinal (GI) ulceration and bleeding [1,2,3]. It is necessary to increase the solubility and dissolution rate of CLC for the patients to achieve immediate pain relief after oral administration. Many pharmaceutical scientists have attempted to improve the oral bioavailability of poorly soluble drugs using various pharmaceutical formulations such as liposomes, mixed micelles, and micro-/nano-emulsions as well as solid dispersion (SD) systems [7,8,9]. Among the various formulations described above, SD systems refer to a technique that produces the homogeneous molecular dispersion of hydrophobic drugs in an inert polymeric carrier to alter the crystalline state of the drugs to an amorphous state, which facilitates the fast dissolution of the drugs [5,6,10,11,12,13,14,15,16]

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