A new approach: Enhancement of solubility of rofecoxib

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M V Ramana
M Himaja
Kamal Dua
V K Sharma
Kavita Pabreja


The present study is aimed at improving the dissolution of poorly soluble drug, rofecoxib. Rofecoxib, being a drug,
basic in nature shows a better solubility in acidic environment. Hence, an attempt was made to provide an acidic
microenvironment around the drug molecules by incorporating various freely soluble acidic substances. Addition of such
additives provides a dual effect of not only providing an acidic microenvironment but also imparts solubilizing effects due to
the free water-soluble nature of the additives used. In the present work, β-cyclodextrin (β-CD) complexes of rofecoxib were
prepared and solubilizing additives such as citric acid and ascorbic acid were incorporated in various proportions. Dissolution
studies were performed in both HCl buffer (pH 1.2) and phosphate buffer (pH 7.4). The results have shown an enhanced
dissolution rate of rofecoxib in both media from beta-cyclodextrin. complex, and a further enhancement of dissolution was found in presence of ascorbic acid as well as citric acid. Differential scanning calorimetery (DSC) and infrared spectroscopy (IR) spectral studies performed on the solid complexes have shown that there is no interaction of the drug with β-CD and the additives. Hence, β-CD enhances the solubility of rofecoxib, and by creating an acidic microenvironment around the drug molecules, solubility of rofecoxib can be enhanced further, which in turn will enhance the absorption of rofecoxib and
produce a better pharmacological activity.
Key words: acidic microenvironment, ascorbic acid, β-cyclodextrin, citric acid, dissolution rate, rofecoxib, solubility


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Ramana, M. V., Himaja, M., Dua, K., Sharma, V. K., & Pabreja, K. (2014). A new approach: Enhancement of solubility of rofecoxib. Asian Journal of Pharmaceutics (AJP), 2(2). https://doi.org/10.22377/ajp.v2i2.330


Hirayama F, Uekama K. Cyclodextrin-based controlled drug release

system. Adv Drug Deliv Rev 1999;36:125-41.

Montassier P, Duchene D, Poelman. Inclusion complexes of tretinoin

with cyclodextrins. Int J Pharm 1997;153:199-209.

Wong JW, Yeun KH. Improved oral bioavailability of artemisinin through

inclusion complexation with beta- and gamma-cyclodextrins. Int J Pharm


Loftsson T, Brewster M. Pharmaceutical applications of cyclodextrins.

Drug solubilization and stabilization. J Pharm Sci 1996;85:


Waleczek KJ, Cabral Marques HM, Hempel B, Schmidt PC. Phase

solubility studies of pure (-)-alpha-bisabolol and camomile essential

oil with beta-cyclodextrin. Eur J Pharm Biopharm 2003;55:247-51.

Martin A, Bustamante P, Chun AH. Physical pharmacy: Physical chemical

principles in the pharmaceutical sciences. New Delhi: B.I. Waverly Pvt

Ltd; 1994. p. 257.

Mishra PR, Mishra M, Jain NK. Pharmaceutical potential of cyclodextrins.

Indian J Pharm Sci 1999;61:193-6.

Florey K. Analytical profiles of drug substances. New York: Academic

Press Inc; 2004. p. 577.

Rajewski RA, Stella VJ. Pharmaceutical applications of cyclodextrins:

, In vivo drug delivery. J Pharm Sci 1996;85:1142-69.

Vane JR, Botting RM. Mechanism of action of aspirin-like drugs. Semin

Arthritis Rheum 1997;26:2-10.

Furst DE. Meloxicam: selective COX-2 inhibition in clinical practice.

Semin Artritis Rheum 1997;26:21-7.

Hawkey CJ, Jackson LM, Harper E, Simon TU, Martensen K, Lines CR.

Review article: the gastrointestinal safety profile of rofecoxib, a highly

selective inhibitor of cyclooxygenase-2, in humans. Aliment Pharmacol

Ther 2001;15:1-9.

Nobel Sl, King DS, Olutade JI. Cyclooxygenase-2 enzyme inhibitors:

place in therapy. Am Fam Physician 2001;61:S669.

Vane JR, Botting RM. Anti-inflammatory drugs and their mechanism of

action. Semin Inflam Res 1998;47:S78.

Vane JR, Botting RM. Mechanism of action of anti-inflammatory drugs.

Semin J Rheumatol Suppl 1996;102:9-21.

Jackson lM, Hawkey CJ. COX-2 selective nonsteroidal anti- inflammatory

drugs: do they really offer any advantages? Drugs 2000;59:1209.

Hawkey CJ. COX-2 inhibitors. Lancet 1999;353:307-14.

Piel G, Pirotte B, Delneuville INeven P, Liabress G, Delarge J, Delattre L.

Study of the influence of both cyclodextrins and L-lysine on the aqueous

solubility of nimesulide: Isolation and characterization of nimesulide-

L-lysine-cyclodextrin complexes. J Pharm Sci 1997;86:475-80.

Chowdary KP, Reddy Kamlakar G. Investigation of complexation of

nimodipine with β-and hydroxypropyl β-cyclodextrins Indian drugs

, vol. 38, no11, pp. 555-558 .

Higuchi T, Connors KA. Phase solubility techniques. Adv Anal Chem

Instr 1965;4:117-212.

Kikuchi M, Hirayama F, Uekama K. Improvement of oral and

rectal bioavailability of carmofur by methylated β-Cyclodextrin

Complexations. Int J Pharm 1987;38:191-8.

Lachman L, Lieberman HA, Kanig JL. The theory and practice of industrial

pharmacy. Philadelphia, USA: Lia and Febiger; 1991. p. 181-2.

Oda M, Saitoh H, Kobayashi M. Aungst BJ. Beta-cyclodextrin as a suitable

solubilizing agent for in situ absorption study of poorly water-soluble

drugs. Int J Pharm 2004;280:95-102.

Vogel Gerhard H. Drug discovery and evaluation: Pharmacological assays.

nd ed. New York: Springer-Verlag Berlin Heidelberg; 2002. p. 716.