Oral-based controlled release formulations using poly(acrylic acid) microgels

Abstract

Aim: To investigate the release of hydrophobic and hydrophilic substances from tablets containing Pemulen and Carbopol as excipients. Method: The dissolution patterns of a hydrophobic (diazepam) and a hydrophilic active substance (midodrine-HCl) from different tablet formulations containing a nonmodified polyacrylic microgel (Carbopol 981 F) or a hydrophobically modified polyacrylic microgel (Pemulen®) have been studied. Possible differences in dissolution in phosphate buffer (pH 6.8) and in 0.1 M HCl between tablets produced using wet granulation and direct compression were also investigated. Results: Tablets produced by wet granulation had a greater effect on the release of active substance from the tablets. No major differences were observed in the release patterns of the hydrophilic substance midodrine-HCl from wet granulated tablets based on Carbopol and Pemulen. However, the release pattern of the more hydrophobic drug substance, diazepam, differed considerably between the two polymers. Wet granulation gave reproducible release patterns. The release patterns from the polymers differed considerably at pH 6.8 but were similar at low pH. Conclusions: The release of the diazepam from the hydrophobic polymer Pemulen was very slow, and the release was close to zero order.

Keywords:

• Carbopol
• controlled release tablets
• cross-linked poly(acrylic acid) microgels
• dissolution kinetics
• Pemulen

Acknowledgments

We are grateful to Diana W Sörensen and Pernille Nybo for technical support during tablet manufacturing, and to Else Thiesen for the analytical work. We would also like to acknowledge the financial support of VINNOVA and Ehrvervsfremstyrelsen through the ELF consortium.

Declaration of interest: The authors report no conflicts of interest.