Abstract
Nifedipine (NIF) is a 1,4-dihydropyridine-based calcium channel blocker with poor solubility, whose bioavailability is highly dependent on the type of formulation. Dry powder mixtures of 20% w/w NIF with microcrystalline cellulose (MCC) and its high surface area nanocellulose analogue, which is namely Cladophora (CLAD) cellulose, were produced by heating at the melting temperature of the drug for 1 h. Non-heated samples were used as a reference. The solid-state properties of the mixtures were characterized by scanning electron microscopy, differential scanning calorimetry and X-ray diffraction. The drug release was studied in biorelevant media, including simulated gastric fluid (SGF), fasted-state simulated intestinal fluid (FaSIF) and fed-state simulated intestinal fluid (FeSIF). An enhanced apparent solubility and faster dissolution rate of NIF were observed in the heated mixture of NIF with CLAD-H in all tested biorelevant media (i.e., SGF, FaSIF and FeSIF), which was due to NIF amorphization in the high surface area nanocellulose powder. Ordinary MCC, which is essentially non-porous, did not produce an enhancement of a similar magnitude. The results of the study suggest that dry powder formulation using high surface area nanocellulose is a facile new strategy for formulating calcium channel blocker drugs, which could potentially be a viable alternative to currently used soft gel liquid capsules.
Highlights
Nifedipine (NIF) is a BCS class II drug with solubility-limited bioavailability
Nanocellulose can produce stronger tablets during direct compression compared to microcrystalline cellulose (MCC) [22,23] and it can be used as a carrier of liquid drugs [24]
We have recently shown that the formulation of ibuprofen and other arylpropionic acid derivatives with nanocellulose can result in enhanced solubility and rapid dissolution rate due to amorphization of the drug [30]
Summary
Nifedipine (NIF) is a BCS class II drug with solubility-limited bioavailability. it experiences substantial first-pass metabolism in liver (42–56%). The amorphization of NIF in mixtures with microcrystalline cellulose (MCC) and its high surface area analogue in the form of nanocellulose is explored. Nanocellulose can produce stronger tablets during direct compression compared to MCC [22,23] and it can be used as a carrier of liquid drugs [24]. We have recently shown that the formulation of ibuprofen and other arylpropionic acid derivatives with nanocellulose can result in enhanced solubility and rapid dissolution rate due to amorphization of the drug [30]. We continue exploring the formulation of poorly soluble drugs from various pharmacological classes with high surface area nanocellulose. We demonstrate how the solubility and dissolution rate of NIF can be substantially increased in dry powder mixtures with high surface area nanocellulose
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