Amorphous solid dispersion with increased gastric solubility in tandem with oral disintegrating tablets: a successful approach to improve the bioavailability of atorvastatin.
BACKGROUND
Serious efforts have been made to overcome the bioavailability problems of ever increasing number of poorly soluble drugs, including atorvastatin (ATO); however, enhancing its gastric solubility has not received much attention.


OBJECTIVE
To improve the bioavailability of ATO by increasing its gastric solubility in a stable oral disintegration tablet (ODT) formulation.


METHODS
Amorphous solid dispersion (ASD) of ATO with Eudragit® EPO was used as API in ODT formulation. Characterization using Differential scanning calorimetry, Powder X-ray diffraction, Fourier transform infrared drug-polymer interaction simulated by molecular modeling, solubility, dissolution and stability studies together with in vivo evaluation.


CONCLUSIONS
In ASD there was uniform distribution of drug in the polymer and it retained the amorphous nature without any chemical interactions except the possibility of hydrogen bond formation, with substantially higher gastric solubility. The dissolution profile of the ODT containing ASD was significantly improved >90% within 15 min compared with 25% of plain ATO formulation. In vivo results showed an overall enhancement in the apparent bioavailability (83% and 434% more than Lipitor® and plain amorphous ATO tablets, respectively). Combining the ASD with ODT presents a reliable solution to overcome the low solubility and bioavailability problems of ATO in a simple, robust and cost effective formulation.
Department of Pharmaceutics, China Pharmaceutical University , Nanjing , People's Republic of China .
Jumah Masoud M
JM
Salmani
Huixia
H
Lv
Sajid
S
Asghar
Jianping
J
Zhou
D000284:Administration, Oral; D000818:Animals; D000924:Anticholesteremic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D000069059:Atorvastatin / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D065569:Gastrointestinal Absorption; D006860:Hydrogen Bonding; D008297:Male; D008958:Models, Molecular; D011109:Polymethacrylic Acids / Q000737:chemistry; D033362:Powder Diffraction; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013607:Tablets; D014961:X-Ray Diffraction
D000924:Anticholesteremic Agents; D005079:Excipients; D011109:Polymethacrylic Acids; D013607:Tablets; C518398:Eudragit E PO; D000069059:Atorvastatin
Atorvastatin; Eudragit EPO; co-precipitation; dissolution; hydrogen bonding; stability