Preparation of Multiparticulate Vaginal Tablet Using Glyceryl Monooleate for Sustained Progesterone Delivery

• Published in: Pharmaceutical development and technology 2009, Vol.14 (1), p.41-52
• Main Authors: Biradar, Shailesh V., Dhumal, Ravindra S., Shah, Manish H., Paradkar, Anant R., Yamamura, Shigeo
• Format: Article
• Language: English
• Subjects: Absorption; Adhesiveness; Animals; Biological and medical sciences; Cattle; cubic phase; Delayed-Action Preparations - administration & dosage; Delayed-Action Preparations - chemistry; Drug Compounding - methods; Excipients - chemistry; Female; General pharmacology; Glycerides - chemistry; Glycerides - pharmacokinetics; glyceryl monooleate; Hydrophobic and Hydrophilic Interactions; Medical sciences; Microscopy, Electron, Scanning - methods; Microscopy, Polarization - methods; multiparticulate bioadhesive tablet; Particle Size; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; progesterone; Progesterone - administration & dosage; Progesterone - chemistry; Rheology - methods; Solvents - chemistry; Spectroscopy, Fourier Transform Infrared - methods; vaginal; Vaginal Creams, Foams, and Jellies - chemistry; Water - chemistry
• ISSN: 1083-7450; 1097-9867
• DOI: 10.1080/10837450802409396

Most of the sustained release vaginal formulations are in the form of bioadhesive gels and tablets. Though proved efficient, their presence in the vagina for a longer time as a bulk produces discomfort and interference with body functioning including sexual activities. Hence, they lack complete patient compliance. In this study, multiparticulate vaginal tablets were prepared by utilizing progesterone (PRO) loaded dry powder precursor of cubic phase (DPPCP) of glyceryl monooleate (GMO). DPPCP were obtained by spray drying GMO with magnesium trisilicate (MTS) and have presented PRO sustained release in simulated vaginal fluid (SVF) for 14 hours. The effect of hydrophilic and hydrophobic tableting excipients on compression, phase, bioadhesion and drug release properties of prepared tablets was evaluated. The effervescent hydrophilic tablet (EHT) prepared with hydrophilic excipients showed rapid disintegration but, diminished sustaining ability owing to transformation into lamellar phase whereas the multiparticulate hydrophobic tablet (MHT) obtained from hydrophobic excipients presented both rapid disintegration and sustained release in SVF by virtue of cubic phase retention. During bioadhesivity testing, fast disintegration of MHT with formation of uniform and viscous bioadhesive layer on cow mucosa was observed even with a small volume of SVF. As MHT may not produce discomfort and interference, it will be preferred over bioadhesive gel or tablet.