Preliminary evaluation of the in vitro release and in vivo absorption in rabbits of the modified-release dosage forms.
OBJECTIVE
The suitability of the rabbit as an animal model for the primary screening and selection of the pilot scale batches during the early stages of the formulation development was studied.


METHODS
Three modified-release formulations of aminophylline consisted of Carbopol® 971P/HPMC K4M (F-I), and HPMC K100M (F-II) or HPMC K4M (F-III) were used. Commercial products were Aminofilin retard 350 mg tablets, Srbolek, Serbia (R-I) and Phyllocontin(®) 350, tablets Purdue Frederic, Canada (R-II).


RESULTS
Calculated release rate constants and the ƒ2 values between R-I/F-I (84.1) and R-II/F-III (83.4) indicated similar in vitro release while the coefficient n showed presence of different mechanisms of release from Anomalous transport, Fickian diffusion to Case-II transport. Higher Tmax, was found in the rabbits, dosed with F-II (12.00 h), F-III (10.50 h), and R-II (15.00 h) formulation. The highest Cmax (9.22 mg/L) was obtained with F-II, similar lower values was seen for F-I and F-III, while commercial products showed the lowest values R-I (5.58 mg/L) and R-II (4.18 mg/L). Higher AUC values were detected for all three formulations (from 115.90 to 204.06 mgh/L) in relation to commercial products (105.33 and 113.25 mgh/L).


CONCLUSIONS
The results demonstrated a good correlation of Level A (r(2) = 0.97) for the two formulations (F-I, F-III) and commercial product (R-I) indicates that there is a reasonable assumption that the rabbit might be use as a model for the preliminary comparison of scale up formulations in the early stages of the product development.
Galenika a.d., Institute for Research and Development, Batajnicki drum b.b, Belgrade, Serbia.
Aleksandra A
AA
Petrovic
Sasa M
SM
Petricevic
Slavica M
SM
Ristic
Svetlana R
SR
Ibric
Slobodanka S
SS
Simic
Zorica R
ZR
Djuric
Radmila B
RB
Popovic
D000284:Administration, Oral; D000628:Aminophylline / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry; D000818:Animals; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry / Q000378:metabolism*; D004304:Dosage Forms; D004353:Drug Evaluation, Preclinical; D007408:Intestinal Absorption / Q000187:drug effects / Q000502:physiology*; D011817:Rabbits; D013607:Tablets
D003692:Delayed-Action Preparations; D004304:Dosage Forms; D013607:Tablets; D000628:Aminophylline