In vitro and in vivo pharmacoscintigraphic evaluation of ibuprofen hypromellose and gelatin capsules.
OBJECTIVE
To evaluate the in vitro and in vivo characteristics of hypromellose (HPMC) capsules prepared using a gellan gum and potassium gelling system compared to conventional hard gelatin capsules.


METHODS
The in vitro dissolution of ibuprofen gelatin and HPMC capsules was determined using the USP and TRIS buffers at pH 7.2. The effect of pH and composition of the media was determined using a model drug that is soluble throughout the pH range 1.2 to 7.2. In an 11 subject four-way crossover study, the gastrointestinal performance of ibuprofen gelatin and HPMC capsule formulations was evaluated using scintigraphy and pharmacokinetics following fasted and fed dosing.


RESULTS
Acid conditions and the presence of K+ cations hinder HPMC capsule opening, whereas in water, dissolution is identical to that of gelatin. These effects are related to the nature of the gel network that is formed in the presence of cations. No significant difference in esophageal transit was observed. Although the in vivo opening times of HPMC capsules were longer than for their gelatin counterparts, no significant difference in the regulatory important pharmacokinetic metrics of C(max) and AUC was found between ibuprofen, gelatin and HPMC capsules.


CONCLUSIONS
The in vitro performance of HPMC capsules differ from gelatin, which will require modification to dissolution testing methodology for certain drugs. However, for the class II BCS drug ibuprofen, the two capsule types were not statistically different when comparing AUC and C(max) values, which suggests that the in vitro differences have reduced in vivo relevance.
Cole
Ewart T
ET
Capsugel AG (A Division of Pfizer), CH-4144 Arlesheim, Basel, Switzerland. ewart.cole@pfizer.com
Scott
Robert A
RA
Cade
Dominique
D
Connor
Alyson L
AL
Wilding
Ian R
IR
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001702:Biopharmaceutics; D002214:Capsules; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D018592:Cross-Over Studies; D004947:Esophagus / Q000000981:diagnostic imaging / Q000502:physiology; D005079:Excipients; D005260:Female; D005746:Gastric Emptying / Q000502:physiology; D005772:Gastrointestinal Transit; D005780:Gelatin; D006801:Humans; D065347:Hypromellose Derivatives; D007052:Ibuprofen / Q000493:pharmacokinetics*; D007205:Indium Radioisotopes; D007553:Isotope Labeling; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives*; D011877:Radionuclide Imaging; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D013270:Stomach / Q000000981:diagnostic imaging; D016284:Technetium Tc 99m Pentetate
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D005079:Excipients; D007205:Indium Radioisotopes; D065347:Hypromellose Derivatives; D002351:Carrageenan; D005780:Gelatin; D008747:Methylcellulose; D016284:Technetium Tc 99m Pentetate; D007052:Ibuprofen