DEVELOPMENT OF TRANSDERMAL DOSAGE FORM USING COPROCESSED EXCIPIENTS OF XANTHAN GUM AND CROSS-LINKED AMYLOSE: IN VITRO AND IN VIVO STUDIES
Keywords:Amylose, Xanthan gum, Coprocessed excipient, Transdermal hydrogel, In vitro penetration, In vivo penetration
Objective: A transdermal hydrogel dosage form consists of a three-dimensional polymer network that binds water in large quantities and is used
for drug delivery. The study’s aim was to prepare coprocessed excipients as a matrix for a transdermal hydrogel containing diclofenac sodium and
examine in vitro and in vivo drug penetrations.
Methods: Four types of coprocessed excipients were produced using two methods that combined crosslinking and coprocessing steps. The produced
excipients were formulated as transdermal gels containing sodium diclofenac. An in vitro penetration test was then performed using a Franz diffusion
cell to pass the drug through a rat skin membrane. An in vivo penetration test was performed by applying the hydrogel to the abdominal skin of male
Sprague-Dawley rats and then measuring the plasma drug concentration.
Results: In vitro penetration results showed that the flux from Co-CLA6-XG 1:2, Co-CLA12-XG 1:2, CL6-Co-A-XG 1:2, and CL12-Co-A-XG 1:2 transdermal
hydrogels was 655.23±116.43 μg∙cm−2/h, 569.08±26.58 μg∙cm−2/h, 867.42±101.27 μg∙cm−2/h−1, and 736.99±15.39 μg∙cm−2/h−1. The in vivo study
resulted in area under the curve for the Co−CLA6−XG 1:2, Co−CLA12−XG 1:2, CL6−Co−A−XG 1:2, and CL12−Co−A−XG 1:2 transdermal hydrogels was
32.08±5.40 μg∙ml−1∙h, 34.27±8.34 μg/ml∙h, 6.20±2.90 μg/ml∙h, and 14.38±2.38 μg/mL∙h, respectively.
Conclusion: The study results showed that the excipients could be processed to form a matrix within a transdermal hydrogel formulation and deliver
sodium diclofenac into systemic circulation in a controlled release manner.
CRC Press; 2004.
2. Kadam AS, Ratnaparkhi MP, Chaudhary SP. Transdermal drug
delivery : An overview. Int J Res Dev Pharm Life Sci 2014;3:1042-53.
3. Peppas NA, Buri PA. Surface, interfacial and molecular aspects of
polymer bioadhesion on soft tissues. J Control Release 1985;2:257-75.
4. Nachaegari SK, Bansal AK. Coprocessed excipients for solid dosage
forms. Pharm Tech 2004;28:52-64.
5. Onofre F, Wang YJ, Mauromoustakos A. Effects of structure and
modification on sustained release properties of starches. Carbohydr
6. Rowe RC, Sheskey PJ, Owen SC. Handbook of Pharmaceutical
Excipients. 5th ed. Washington, DC: Pharmaceutical Press and American
Pharmacist Association; 2006.
7. Surini S, Ariani L, Putri KS, Hayun H, Anwar E. Coprocessed
excipients of crossliked amylose and xanthan gum for use in controlled
release dosage forms. Int J App Pharm 2018;10:59-65.
8. Witt K, Bucks D. Studying in vitro skin penetration and drug release to
optimize dermatological formulations. In: Pharmaceutical Technology.
New York: Anvastar Communication Inc.; 2003.
9. Cury BS, Klein SI, Evangelista RC. Modeling a system of phosphated
cross-linked high amylose for controlled drug release. Part 1: Synthesis
and polymer characterization. React Funct Polym 2009;68:1200-6.
10. Marthur A. Studies on Phosphorylation Status of Starch in Potato
Tubers (Solanum tuberosum L.). Dissertation. Patiala: Department
of Biotechnology and Environmental Sciences Thapar Institute of
Engineering and Technology Patiala; 2003.
11. Paschall FE. Phosphorylation with Inorganic Phosphate Salts.
New York: Academic Press; 1964.
12. Klimes J, Sochor J, Dolezal P, Körner J. HPLC evaluation of diclofenac
in transdermal therapeutic preparations. Int J Pharm 2001;217:153-60.
13. Sintov AC, Botner S. Transdermal drug delivery using microemulsion
and aqueous systems: Influence of skin storage conditions on the
in vitro permeability of diclofenac from aqueous vehicle systems. Int J
14. European Medicines Agency. Guideline on Bioanalytical Method
Validation; 2011. Available from: http://www.ema.europa.eu/docs/en_
15. Murphy J, Riley JP. A modified single-solution method for the determination
of phosphorus in natural waters. Anal. Chim. Acta 1962;27:31-6.
16. Bhanja S, Kishore P, Das AK, Secunderabad M, Pradesh A. Formulation
and evaluation of diclofenac transdermal gel. J Adv Pharm Educ Res
17. Sherman P. Techniques for assessing the rheological properties of
toiletry and cosmetic products. J Soc Cosmet Chem 1966;17:439-65.
18. Shargel L, Andrew BC, Wu-Pong S. Applied Biopharmaceutics
and Pharmacokinetics. 5th ed. United States: McGraw-Hill Access
19. Dumoulin Y, Alex S, Szabo P, Cartilier L, Mateescu MA. Crosslinked
amylose as matrix for drug controlled release. X-ray and FT-IR
structural analysis. Carbohydr. Polym. 1998;37:361-70.
20. Lenaerts V, Beck RH, Van Bogaert E, Chouinard F, Höpcke R,
Désévaux C. Cross-linked High Amylose Starch for Use in Controlledrelease
Pharmaceutical Formulations and Processes for its Manufacture.
United States Patent US No. 6, 607; 2003.
21. Fini A, Bassini G, Monastero A, Cavallari C. Diclofenak salts, VIII.
Effect of the counterions on the permeation through porcine membrane
from aqueous saturated solutions. Pharmaceutics 2012;4:413-29.