NIFEDIPINE

Nifedipine is a BCS class II poor soluble drug with poor oral bioavailability and substantial first-pass metabolism in liver. It is mainly used to treat cardiovascular diseases such as hypertensive crises, angina pectoris, and chronic hypertension. Nifedipine formulations exist in a variety of forms including immediate, retarded, and extended release formulations. Pharmacokinetics of nifedipine is highly influenced by formulation. The first formulations of nifedipine were immediate release soft gel caspules (Adalat), followed by retarded action tablets, and, finally, extended release osmotic pump tablets. Soft gel capsules of nifedipine (e.g. Adalat) are still common. Choosing between immediate and modified release formulations, considerations for dose and daily intake frequency should be taken, i.e. immediate release formulations are prescribed in low doses (5-10 mg) 3 times a day, while extended release tablets as a single high-dose formulation with maximum allowable daily dose of 60 mg. Nifedipine is practically insoluble in water and, thereby, belongs to problem drugs. The most common immediate release dosage forms of nifedipine include soft gel capsules and film-coated tablets. Absorption of nifedipine is rapid and complete from GIT following oral administration. The rate and extent of absorption from film-coated tablets is slower than that from soft gel capsules, which is around 1.6 h for soft gel capsules and 4.2 h for film-coated tablets, respectively. It should however be mentioned that Tmax for soft gel capsules could show high variability as values between 0.25 and 2.9 h have been reported. Following rapid absorption, nifedipine undergoes significant first-pass metabolism in liver, and the absolute bioavailability ranges between 42 and 56%. 

Our solution: Our data, including solid-state characterizations and in vitro drug release in biorelevant media (SGF, FaSIF and FeSIF), show that we can achieve enhanced solubility and more rapid dissolution from dry powder formulations compared to conventional form. The enhancement in solubility is 3-fold and is observed in all biorelevant media. This represents a viable cost-efficient alternative to currently used soft gel capsules. Furthermore, the concept could be projected to other substances from this pharmacological class currently formulated in the form of a salt, e.g. felodipine, amlodipine mesylate or besylate.