Sustained release dosage form of noscapine HCl using hot melt extrusion (HME) technique: formulation and pharmacokinetic
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ORIGINAL ARTICLE
Sustained release dosage form of noscapine HCl using hot melt extrusion (HME) technique: formulation and pharmacokinetics Arvind Bagde 1 & Nilkumar Patel 1 & Ketan Patel 1,2 & Ebony Nottingham 1 & Mandip Singh 1
# Controlled Release Society 2020
Abstract Sustained release formulation of noscapine (Nos) HCl could be useful in maintaining plasma Nos HCl level for prolonged period of time, which is important for chemo-sensitization. However, weakly basic drugs like Nos HCl have pH-dependent solubility. Therefore, the purpose of this study was to achieve pH-independent drug release by developing the sustained release dosage form of Nos HCl using biodegradable polymer Eudragit RLPO and FDA-approved pH modifier citric acid (CA) by hot melt extrusion (HME) technique. Nos HCl was successfully formulated using 10% CA with 91.2 ± 1.34% drug recovery through the extruder. X-ray diffraction (XRD) results showed that drug was completely dispersed in the polymer and changed to amorphous from its crystalline form. In vitro drug release studies in pH 6.8 buffer showed that formulation containing 10% CA released 70.99 ± 3.85% drug in 24 h after initial burst release of 40.04 ± 2.39% compared to formulation without CA. Furthermore, in vivo pharmacokinetic data showed the sustained release plasma concentration time curve with significant (p < 0.05) increase in area under curve (AUC) in Nos HCl extrudate compared to Nos HCl solution. Overall, HME can be used to enhance the bioavailability and achieve the pH-independent solubility of weakly basic drugs like Nos HCl. Keywords Hot melt extrusion . Sustained release formulation . Noscapine HCl . Weakly basic drug . Solid dispersion
Introduction Several drugs which are weak bases or their salts have pHdependent solubility. Such drugs are less soluble in basic pH compared to acidic pH environment. Therefore, these drugs show the variability in their release pattern in different pH buffers in vitro. These variabilities are important in in vivo studies and may cause inter- and intra-individual differences in bioavailability and plasma profiles [1, 2]. Various researchers have reported that increased pH in GI tract results in incomplete absorption of several basic drugs
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s13346-020-00838-w) contains supplementary material, which is available to authorized users. * Mandip Singh [email protected] 1
College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA
2
College of Pharmacy and Health Sciences, St. John’s University, Queens, NY 11439, USA
including rifampicin, ketoconazole, and dipyridamole [2]. So far, numerous methodologies have been reported to address the issue of pH-dependent solubility of weakly basic drugs. Dashevsky et al. demonstrated that the use of extended and enteric release polymers as film-coating materials can attain pH-independent drug release in which they showed that enteric polymer has low solubility in aci
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