Formulation of enterosoluble microparticles for an acid labile protein.
OBJECTIVE
A microencapsulation method that preserves the activity of an acid labile protein was developed.


METHODS
Solvent evaporation technique that employed ICH class 2 and 3 solvents methanol and acetone, respectively to dissolve pH-sensitive Eudragit polymers was investigated. Total protein released and lactase activities were measured using the USP method A for enteric cores and optimized with respect to process parameters.


RESULTS
The percentage yields and entrapment efficiencies were directly proportional to solid content. The mean percentage yield and entrapment efficiency of selected sample was 84 +/- 0.9% and 88 +/- 0.7%, respectively. The residual specific activity of lactase in the selected sample was 89% +/- 0.8 with a net activity loss of 2 +/- 0.28% and 4 +/- 0.52% under ambient and stressed storage, respectively. Dibutyl sebacate levels, lower processing temperatures and lower processing speeds were influential in modulating enzyme activity. The most important formulation factor affecting lactase stability was Eudragit type, followed in decreasing order by processing temperature, processing speed, and solid percentage.


CONCLUSIONS
Reliable control of lactase release was achieved by microencapsulating the enzyme with pH-sensitive Eudragit L and S enteric polymers using either acetone- or methanol-based solvent but lactase activity was preserved only in acetone-based formulations.
Alavi
Ahmed Kashif
AK
Pharmacy and Administrative Sciences, College of Pharmacy, St. John's University, New York 11439, USA. squillae@stjohns.edu
Squillante
Emilio
E
Mehta
Ketan A
KA
D000096:Acetone / Q000737:chemistry; D000143:Acids / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D000432:Methanol / Q000737:chemistry; D008855:Microscopy, Electron, Scanning / Q000379:methods; D011109:Polymethacrylic Acids / Q000737:chemistry; D011506:Proteins / Q000737:chemistry*; D012107:Research Design; D012995:Solubility; D012997:Solvents / Q000737:chemistry
D000143:Acids; D011109:Polymethacrylic Acids; D011506:Proteins; D012997:Solvents; D000096:Acetone; C038300:methylmethacrylate-methacrylic acid copolymer; D000432:Methanol