Download Developing of solid lipid based formulations for

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the work of artificial intelligence, which forms the content of this project

Document related concepts
no text concepts found
Transcript 
Developing of solid lipid based formulations for enhancement of ibuprofen
solubility
M.G. Gordienko, E.A. Ershova, K. Kalyanova, N.V. Menshutina, D.U. Zhukov Mendeleyev
University of Chemical Technology of Russia, CAPE Dep., Geroev Panfilovtsev 20, 125480
Moscow, Russian Federation; tel. +74954950029, e-mail: [email protected].
Although oral delivery is the most preferred method of drug administration, this is not
possible for roughly 50% of currently marketed drug compounds due to their low solubility in
water and low oral bioavailability. Recent approaches to address this problem include
administration of drug components with lipid vehicles such as oils, liposomes, and selfemulsifying formulations. The paper deals with an investigation and development of lipid
based formulations to enhance the solubility of the active pharmaceutical ingredients (API) of
the II class in correspondence to BCS. The release of these substances from the dosage form
is the rate-limiting step for their introduction into the systemic blood circulation. Ibuprofen
was selected as a model substance. It has poor solubility in an acidic buffer and good in
phosphate. At the first stage of research the solubility of ibuprofen was determined in several
excipients for lipid based formulations. The Table 1 shows the characteristics of the
excipients as well as the ibuprofen solubility (IS) at them.
Table 1. The characteristics of the excipients and the ibuprofen solubility
Excipient
Chemical description
HLB IS, g/g
Labrasol
Caprylocaproyl macrogol-8 glycerides EP / 14
0.332
caprylocaproyl polyoxyl-8 glycerides NF
Gelucire 44/14
Lauroyl macrogol-32 glycerides EP / lauroyl 14
0.003
polyoxyl-32 glycerides NF
Plurol Oleique CC497 Polyglyceryl 3 dioleate
6
0.005
Lauroglycol 90
Propylene glycol monolaurate (type II) EP/NF
5
0.188
Plurol Diisostearique Triglycerol diisostearate EP/NF
4.5
0.005
Labrafil M 2125 CS
Linoleoyl macrogol-6 glycerides EP / linoleoyl 4
0.115
polyoxyl-6 glycerides NF
Labrafil M 1944 CS
Oleoyl macrogol-6 glycerides EP / oleoyl 4
0.003
polyoxyl-6 glycerides NF
Labrafaс PG
Propylene glycol dicaprylocaprate EP / 2
0.205
Propylene glycol dicaprylate/dicaprate NF
Labrafac
Lipophile Triglycerides medium-chain EP / medium-chain 1
0.100
WL 1349
triglycerides NF
Based on the analysis of the data the Labrasol, Labrafac PG, Lauroglycol 90, Labrafil M
2125 CS were selected for further research. These products are liquid at ambient temperature.
For solid forms (suppositories, pellets or granules) is it possible to use Gelucire 44/14 in
combine with the selected products (case I) or to adsorb the luiqid excipients by
pharmaceutical sorbents (case II). The follow lipid based formulation – Gelucire 44/14/
Lauroglycol 90; Gelucire 44/14/ Labrafil M 2125 CS; Gelucire 44/14/ Labrafaс PG – were
investigated by titration with water and ternary phase diagrams were constructed. Based on the
analysis of ternary phase diagrams the optimal compositions were selected. The solid dosage
forms were obtained for both cases. The ibuprofen release kinetics from solid dosage form
were investigated. The research is supported by the Ministry of High Education and Science
within the framework of basic component of the State Assignment.
Related documents