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Design of Controlled Release System for Paracetamol Based on Modified Lignin.

ABSTRACT: The influence of lignin modification on drug release and pH-dependent releasing behavior of oral solid dosage forms was investigated using three different formulations. The first formulation contains microcrystalline cellulose (MCC 101) as the excipient and paracetamol as the active pharmaceutical ingredient (API). The second formulation includes Alcell lignin and MCC 101 as the excipient and paracetamol, and the third formulation consists of carboxylated Alcell lignin, MCC 101 and paracetamol. Direct compaction was carried out in order to prepare the tablets. Lignin can be readily chemically modified due to the existence of different functional groups in its structure. The focus of this investigation is on lignin carboxylation and its influence on paracetamol control release behavior at varying pH. Results suggest that carboxylated lignin tablets had the highest drug release, which is linked to their faster disintegration and lower tablet hardness.

SUBMITTER: Pishnamazi M

PROVIDER: S-EPMC6630591 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Design of Controlled Release System for Paracetamol Based on Modified Lignin.

Pishnamazi Mahboubeh M Hafizi Hamid H Shirazian Saeed S Culebras Mario M Walker Gavin M GM Collins Maurice N MN

Polymers 20190618 6

The influence of lignin modification on drug release and pH-dependent releasing behavior of oral solid dosage forms was investigated using three different formulations. The first formulation contains microcrystalline cellulose (MCC 101) as the excipient and paracetamol as the active pharmaceutical ingredient (API). The second formulation includes Alcell lignin and MCC 101 as the excipient and paracetamol, and the third formulation consists of carboxylated Alcell lignin, MCC 101 and paracetamol. ...[more]

PMID: 31216694

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Project description:Chitosan nanofibrous membranes have immense potential in tissue engineering and drug delivery applications because of their increased surface area, high degree of biocompatibility, and their ability to mimic the extracellular matrix. However, their use is often limited due to their extreme hydrophilic nature causing them to lose their nanofibrous structure in vivo. In the present study, chitosan membranes were modified either by acylation reactions using fatty acids of different chain lengths or tert-butyloxycarbonyl (tBOC) protecting groups to increase the hydrophobicity of the membranes and protect the nanofibrous structure. The modified membranes were characterized using scanning electron microscopy, attenuated total reflectance Fourier transform infrared spectroscopy, water contact angle and elemental analysis to confirm the addition of the modification groups. These membranes were then evaluated to control the release of a hydrophobic osteogenic drug-simvastatin (SMV). The interaction between SMV and the polymer was determined using molecular modeling. Pure SMV and SMV loaded membranes were examined for their in vitro cytotoxicity and osteogenic potential using preosteoblast mouse bone marrow stromal cells. From results, it was evident that as the fatty acid chain length increased from two to six methylene groups, the hydrophobicity of the membranes increased (59.2 ± 8.2° to 94.3 ± 8.5° water contact angle). The amount of drug released from the membranes could be controlled by changing the amount of initial drug loaded and/or the type of modifications. After 4 weeks, for a 500 μg loading, the short chain fatty acid modified membranes released 17.8 ± 3.2% of the drug whereas a long chain fatty acid released only 4.8 ± 0.8%. Similarly, for a 50 μg loading, short chain modified membranes released more (73.3 ± 33.3%) of the loaded drug as compared to the long chain membranes (43.0 ± 3.5%). The long chain fatty acid membranes released SMV for extended time periods of up to 90 days. This data was further supported by molecular modeling, which revealed that SMV was more compatible with more hydrophobic membranes. Cell studies showed that pure SMV from 75 to 600 ng/ml range possessed osteogenic potential in a dose dependent manner and the amount of SMV released from the most hydrophobic FA treated membranes was not cytotoxic and supported osteogenic differentiation. Therefore, this study demonstrates our ability to control the release of a hydrophobic drug from modified chitosan membranes as per the clinical need.

Dataset Information

Design of Controlled Release System for Paracetamol Based on Modified Lignin.

Publications

Design of Controlled Release System for Paracetamol Based on Modified Lignin.

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