Dear all,Back to the Top
Is the concentration of tween matters in the PK of the drug, as we
found uncertain results when we carried out PK of same NCE two times
(From same Batch) in suspension form.
Fact that i used different concentration of tween 80 (0.1% and 100%).
and same concentration of CMC (0.25%).
Is tween have any effect if use in psycho pharmacological drug
screening as an surfactant for preparing the dosage formulation.
with thanks
Venkatesh.P
Senior Pharmacologist,
Dept of Drug Metabolism and Pharmacokinetics,
Discovery Research, Dr.Reddy's Labs.
Hyderabad, India-500050.
Phone no:91-9849692908
Dear venkatesh,Back to the Top
I feel definitely the more surfactant you use you get different results
possibly due to
1. Tween 80 it self act as a solubilizer as well as wetting agent
2. the more Tween 80, the change in pk could be due to more
solubility rather than suspending the drug.
3. tween 80 if you use more it will cause diarrhorea in rats and mice,
my practical observation which may change your gastric absorption.
My opinion is always try first without Tween 80 and see the suspension
how it is uniform and if prep is not good then try again with 1 or 2
drops of Tween 80 or maximum up to 10% only. Because our objective
should be to get ideal wetting properties in a way to make a uniform
suspension by reducing the contact angle.
I appreciate if more light on this topic in this group.
Regards,
KANTHI KIRAN V.S. VARANASI, M.Pharm, MBA
Sr. Research Scientist,
Drug Metabolism and Pharmacokinetics Department,
Glenmark Pharmaceuticals LTD.
Glenmark Research Centre,
Plot No. A-607, T.T.C Industrial Area,
MIDC, Mahape,
NAVI MUMBAI-400709
INDIA.
Ph.: 91-22-55902491/92 ext 315
Fax: 91-22-55902318
Dear Venkatesh,Back to the Top
Yes, the concentration of tween 80 does matter when
determining the PK of NCE. Several year ago, one my
colleagues examined the effect of various
concentrations of tween 80 on absorption of couple of
compounds and showed that absorption kinetics of a
given compound are different at different tween 80
concentrations.
Rostam
surfactant concentration matters...Back to the Top
see some papers about surfactants and absorption:
Arzneimittelforschung 1999 Jan;49(1):44-50
Experimental studies on the influence of surfactants
on intestinal absorption of drugs. Cefadroxil as model
drug and sodium taurocholate as natural model
surfactant: studies in rat colon and in rat duodenum.
Carmona-Ibanez G, del Val Bermejo-Sanz M, Rius-Alarco
F, Martin-Villodre A.
PMID: 10028379 [PubMed - indexed for MEDLINE]
Arzneimittelforschung 1995 Sep;45(9):1013-7
Experimental studies on the influence of surfactants
on intestinal absorption of drugs. Cefadroxil as model
drug and sodium lauryl sulfate as model surfactant:
studies in rat duodenum. Sancho-Chust V, Bengochea M,
Fabra-Campos S, Casabo VG, Martinez-Camara MJ,
Martin-Villodre A.
PMID: 7488302 [PubMed - indexed for MEDLINE]
Arzneimittelforschung 1995 May;45(5):595-601
Experimental studies on the influence of surfactants
on intestinal absorption of drugs. Cefadroxil as model
drug and sodium lauryl sulfate as model surfactant:
studies in rat colon. Sancho-Chust V, Fabra-Campos S,
Gomez-Meseguer V, Bengochea M, Martin-Villodre A.
PMID: 7612059 [PubMed - indexed for MEDLINE]
Eur J Drug Metab Pharmacokinet 1991;Spec No 3:32-42
Biophysical absorption models for phenyl-alkyl acids
in the absence and in the presence of surfactants.
Studies in the rat small intestine. Fabra-Campos S,
Real JV, Gomez-Meseguer V, Merino M, Pla-Delfina JM.
PMID: 1820901 [PubMed - indexed for MEDLINE
Martin-Algarra RV, Pascual-Costa RM, Merino M, Casabo
VG.
Effects of surfactants on amiodarone intestinal
absorption. I. Sodium laurylsulfate. Pharm Res. 1994
Jul;11(7):1042-7.
PMID: 7937546 [PubMed - indexed for MEDLINE]
Martinez-Coscolla A, Miralles-Loyola E, Garrigues TM,
Sirvent MD, Salinas E, Casabo VG.
Studies on the reliability of a novel
absorption-lipophilicity approach to interpret the
effects of the synthetic surfactants on drug and
xenobiotic absorption. Arzneimittelforschung. 1993
Jun;43(6):699-705.
PMID: 8352827 [PubMed - indexed for MEDLINE]
OUR old papers....
J.M. Pl\0xB7-Delfina, M.D. P\0xC8rez-Buend\0xCCa, V.G. Casab\0xDB,
J.E. Peris-Ribera, E. S\0xB7nchez-Moyano y A.
Mart\0xCCn-Villodre. Absorption-partition relationships
for true homologous series of xenobiotics as a
possible approach to study mechanisms of surfactants
on absorption. I. Aromatic amines in rat colon
International Journal of
Pharmaceutics,37,: 49- 64,1987
E.F. Collado, S. Fabra-Campos, J.E. Peris-Ribera,
V.G. Casab\0xDB, A. Mart\0xCCn-Villodre y J.M. Pl\0xB7-Delfina.
Absorption-partition relationships for true homologous
series of xenobiotics as a possible approach to study
mechanisms of surfactants on absorption. II. Aromatic
amines in rat small intestine. International Journal
of Pharmaceutics,
44,: 187-196,1988.
Absorption-partition Relationships for True Homologous
Series of Xenobiotics as a Possible Approach to Study
Mechanisms of Surfactants in Absorption. IV.
Phenylacetic Acid Derivatives and Anionic
Surfactants." Garrigues T.M., P\0xC8rez-Varona A.T.,
Bermejo M.V., Mart\0xCCn-Villodre A. International Journal
of Pharmaceutics, 79, 135-140 (1992).
Comparison between synthetic and natural...
2. "Compared Effects of Synthetic and Natural Bile
Acid Surfactants on Xenobiotic Absorption. I. Studies
with Polysorbate and Taurocholate in Rat Colon."
Bermejo M.V., P\0xC8rez-Varona A.T., Segura-Bono M.J.,
Mart\0xCCn-Villodre A., Pl\0xB7-Delfina J.M., Garrigues T.M.
International Journal of Pharmaceutics, 69, 221-231
(1991).
5. "Compared Effects of Synthetic and Natural Bile
Acid Surfactant on Xenobiotic Absorption.II. Studies
with sodium glycocholate to confirm a hypothesis."
Garrigues T.M., Segura-Bono M.J., Bermejo M.V., Merino
V., Pl\0xB7-Delfina J.M.
International Journal of Pharmaceutics, 101, 209-217
(1994).
6. "Compared Effects of Synthetic and Natural Bile
Acid Surfactant on Xenobiotic Absorption.III. Studies
with mixed micelles." Segura-Bono M.J., Garrigues
T.M., Merino V., Bermejo M.V. International Journal
of Pharmaceutics, 107, 159-166 (1994).
Fabra Campos S., Climent E., Sanchis Cort\0xC8s A., Pl\0xB7
Delfina J.M. Compared effects of synthetic and natural
bile acid surfactants. IV. Studies with taurocholate
in the rat small intestine. International Journal of
Pharmaceutics, 109, 197-207 (1994).
20. R.V. Mart\0xCCn Algarra, R.M. Pascual Costa, M. Merino
V.G. Casab\0xDB.
Effects of polysorbate 80 on amiodarone intestinal
absorption in the
rat. International Journal of Pharmaceutics.122, 1-
8,1995.
I do not know if you can access easily to this
papers...but if you are interested in some of them,
let me know (mbermejo.-at-.uv.es) and I'll send you a copy.
Sorry for the long mail
hope this helps
Marival Bermejo
http://www.uv.es/~mbermejo/absorption.htm
PharmPK Discussion List Archive Index page
Copyright 1995-2010 David W. A. Bourne (david@boomer.org)