Partitioning Behavior of Gemifloxacin in Anionic, Cationic and Nonanionic Surfactants. Calculation of Dermal Permeability Coefficient

Theophilus C.  Onyekaba; Chika J.  Mbah; Chukwudinma C.  Achilefu

doi:10.4236/pp.2015.64022

Theophilus C. Onyekaba¹, Chukwudinma C. Achilefu², Chika J. Mbah²^*

Abstract: Transdermal delivery acts as an alternative to oral delivery of drugs and possibly provids also an alternative to hypodermic injection. Transdermal delivery when compared to oral route has a variety of advantages namely: avoiding the degradation of drugs in the stomach environment, providing steady plasma levels, avoiding first-pass metabolism, increaseing patient compliance, easy to use, non-invasive and inexpensive, increasing the therapeutic index with a simultaneous decrease in drug side effects. Despite these advantages, one of the greatest challenges to transdermal delivery is that only a limited number of drugs are amenable to administration by this route. Gemifloxacin, a broad spectrum fourth generation quinolone antibacterial agent has pharmacokinetic characteristics (particularly its low maximum plasma concentration, obtained following repeat oral dose of 320 mg) that makes it a potential target for transdermal delivery. The objective of the study was to explore the possibility of surfactants (anionic, cationic and nonionic) acting as dermal enhancers of gemifloxacin assuming that the drug is to be formulated into topical or transdermal pharmaceutical dosage form. To accomplish the objective, gemifloxacin was partitioned between chloroform and surfactants containing varying concentrations of sodium lauryl sulfate, cetyltrimethylammonium bromide, polysorbate-20 and polysorbate-80. The data obtained were used to estimate the dermal permeability coefficient. The partitioning was carried out by shake flask method at room temperature. It was observed that all the surfactants decreased the partition behavior of gemifloxacin when compared to that of water alone. Sodium lauryl sulfate produced the most decreasing partition effect at the highest concentration studied (2% w/v). The permeability coefficient (Kp) was estimated from the partition coefficient data and the molecular weight of the drug. As permeability coefficient is an important descriptor for evaluating dermal absorption of drugs employed in clinical treatment of various dermal accessible ailments, the results of the study suggest that the investigated surfactants might not be potential transdermal enhancers of gemifloxacin.

Keywords: Gemifloxacin, Surfactants, Partition Coefficient

Cite this paper: Onyekaba, T. , Achilefu, C. and Mbah, C. (2015) Partitioning Behavior of Gemifloxacin in Anionic, Cationic and Nonanionic Surfactants. Calculation of Dermal Permeability Coefficient. Pharmacology & Pharmacy, 6, 207-211. doi: 10.4236/pp.2015.64022.

References

[1] Hooper, D.C. (2001) Emerging Mechanisms of Fluoroquinolones Resistance. Emerging Infectious Diseases, 7, 337-341.
http://dx.doi.org/10.3201/eid0702.010239

[2] Oliphant, C.M. and Green, G.M. (2002) Quinolones: A Comprehensive Review. American Family Physician, 65, 455-464.

[3] Montagna, W., Van Scott, E.J. and Stoughton, R.B. (1972) Pharmacology and the Skin. Appleton Century Crafts, New York.

[4] Rutter, N. (1987) Drug Absorption through the Skin; a Mixed Blessing. Archives of Disease in Childhood, 62, 220-221.
http://dx.doi.org/10.1136/adc.62.3.220

[5] Hwang, C.C. and Danti, A.G. (1983) Percutaneous Absorption of Flufenamic Acid in Rabbits. Effect of Dimethylsulfoxide and Various Nonionic Surface Active Agents. Journal of Pharmaceutical Sciences, 72, 857-860.
http://dx.doi.org/10.1002/jps.2600720805

[6] Shen, W.W., Danti, A.G. and Bruscato, F.N. (1976) Effect of Nonionic Surfactants on Percutaneous Absorption of Salicyclic Acid and Sodium Salicylate in the Presence of Dimethylsulfoxide. Journal of Pharmaceutical Sciences, 65, 1780-1783.
http://dx.doi.org/10.1002/jps.2600651222

[7] Mbah, C.J. and Okekearu, L. (2013) Propylene Glycol, Polysorbate-80 and Sodium Lauryl Sulfate as Potential Dermal Absorption Enhancers of Celecoxib. Standard Scientific Research and Essays, 1, 32-35.

[8] Hansch, C. and Dunn III, W.J. (1972) Linear Relationships between Lipophilic Character and Biological Activity of Drugs. Journal of Pharmaceutical Sciences, 61, 1-19.
http://dx.doi.org/10.1002/jps.2600610102

[9] Bawden, D., Gymer, G.E., Marriott, M.S. and Tute, M.S. (1984) Quantitative Structure-Activity Relationships in a Group of Imidazole Antimycotic Agents. The European Journal of Medicinal Chemistry, 18, 91-96.

[10] Bunge, A.L. and Cleek, R. L. (1995) A New Method for Estimating Dermal Absorption from Chemical Exposure. Effect of Molecular Weight and Octanol-Water Partitioning. Pharmaceutical Research, 12, 88-95.
http://dx.doi.org/10.1023/A:1016242821610

[11] (1992) United States Environmental Protection Agency: Dermal Exposure Assessment: Principles and Applications. EPA/600/8-91/011 B.

[12] Karinth, S., Schaller, K.H. and Drexler, H. (2005) Is Permeability Coefficient Kp a Reliable Tool in Percutaneous Absorption Studies. Archives of Toxicology, 79, 155-159.
http://dx.doi.org/10.1007/s00204-004-0618-4

[13] Potts, R.V. and Guy, R.H. (1992) Predicting Skin Permeability. Pharmaceutical Research, 9, 663-669.
http://dx.doi.org/10.1023/A:1015810312465

[14] Gennaro, A.R. (1995) Remington: The Science and Practice of Pharmacy. 19th Edition, Mack Publishing Company, Easton.

[15] Wang, F.A. (2001) Molecular Thermodynamics and Chromatographic Retention. China Meteorology Press, Beijing.

[16] Johansen, M. and Bundgaard, H. (1980) Prodrugs as Drug Delivery Systems XI. Solubility, Dissolution and Partition Behaviour of N-Mannich Bases and N-Hydroxymethyl Derivatives. Arch. Pharm. Chem. Sci. Edu., 8, 141-151.