In situ lyophilisation of nifedipine directly in hard gelatine capsules

• Published in: Pharmaceutical development and technology 2013-12, Vol.18 (6), p.1379-1390
• Main Authors: Crum, Matthew, Elkordy, Amal Ali, Zarara, Moataz, Elkordy, Eman Ali
• Format: Article
• Language: English
• Subjects: Biological Availability; Capsules - chemistry; Chemistry, Pharmaceutical - methods; Co-povidone; dissolution; Excipients - chemistry; F-127; Freeze Drying - methods; Gelatin - chemistry; in situ lyophilisation; inulin; Inulin - chemistry; nifedipine; Nifedipine - chemistry; Pluronic; Poloxamer - chemistry; Povidone - chemistry; Solubility; Solutions - chemistry; Solvents - chemistry
• ISSN: 1083-7450; 1097-9867
• DOI: 10.3109/10837450.2012.723718

Hydrophobic drugs present a challenge due to: (i) adhesion and agglomeration; hence the choice of the suitable processing technique to have the drugs into orally administered dosage forms is critical. (ii) Poor dissolution and poor aqueous solubility; hence poor bioavailability. A novel method which is in situ lyophilisation directly in hard gelatin capsule shells was used in this research to enhance the dissolution of nifedipine (a model hydrophobic drug) in the presence of co-povidone, Pluronic®F-127 and inulin as enhancement excipients (to the best of our knowledge those excipients have not been previously used with nifedipine in lyophilised forms). Solutions of nifedipine and excipients in a range of concentrations (0.5, 1, 5 and 10%w/v) were prepared using a co-solvent system of tert- butyl alcohol/water mixture. These solutions were filled directly into bodies of size 000 hard gelatin capsule shells and freeze dried. Pure drug and all formulations were characterised by solubility, wetting studies and in vitro dissolution. Also, conformational integrity and thermal characteristics of nifedipine formulations were investigated using FT-IR spectroscopy and differential scanning calorimetry (DSC), respectively. The in situ lyophilisation of nifedipine with excipients, looks a promising method not only to improve the hydrophobic drug dissolution but also to be cost effective.