PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of aapspharmspringer.comThis journalToc AlertsSubmit OnlineOpen Choice
 
AAPS PharmSciTech. 2007 March; 8(1): E50–E55.
Published online 2007 January 26. doi:  10.1208/pt0801007
PMCID: PMC2750442

Formulation development and in vitro and in vivo evaluation of membrane-moderated transdermal systems of ampicillin sodium in ethanol: pH 4.7 buffer solvent system

Abstract

The objective of the present study was to develop membrane-moderated transdermal systems of ampicillin sodium and to evaluate them with respect to various in vitro and in vivo parameters. The membrane-type transdermal systems were prepared using a drug with various antinucleant polymers— hydroxypropyl methylcellulose (HPMC), methylcellulose (MC), cellulose acetate phthalate, chitosan, sodium alginate (SA), and sodium carboxymethylcellulose—in an ethanol: pH 4.7 buffer volatile system by the solvent evaporation technique with HPMC as the rate-controlling membrane for all the systems. The swelling properties of the polymers were studied, and drug-polymer interaction studies were performed. The patches were subjected to various physicochemical studies, in vitro release studies, permeation studies, and skin irritation studies. The best patch among the formulations was selected for further in vivo studies. Compared to the other patches, SA exhibited the highest moisture content at 16%; a 21% moisture uptake was found with MC. The release and permeation of the drug from the SA patch was found to be the maximum. The in vivo study of the SA patch exhibited a peak plasma concentration Cmax of 126 μg/mL at Tmax 4 hours. Hence, it can be concluded that hydrophilic ampicillin sodium can be developed as a transdermal delivery system with SA that is an alternative to intravenous administration and has minimal adverse effects.

Keywords: Membrane controlled, hydrophilic polymer, swelling ratio, hydrophilic drug, in vivo study

Full Text

The Full Text of this article is available as a PDF (180K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
1. Oliyai R, Lindenbaum S. Stability testing of pharmaceuticals by isothermal heat conduction calorimetry: ampicillin in aqueous solution. Int J Pharm. 1991;73:33–36. doi: 10.1016/0378-5173(91)90097-8. [Cross Ref]
2. Carafa M, Marianecci C, Lucania G, Marchei E, Santucci E. New vesicular ampicillin-loaded delivery systems for topical application: characterization, in vitro permeation experiments and antimicrobial activity. J Control Release. 2004;95:67–74. doi: 10.1016/j.jconrel.2003.10.022. [PubMed] [Cross Ref]
3. Ahren IL, Karlsson E, Forsgren A, Riesbeck K. Comparison of the antibacterial activities of ampicillin, ciprofloxacin, clarithromycin, telithromycin, and quinupristin/dalfopistin against intracellular non-typeableHaemophilius influenzea. J Antimicrob Chemother. 2002;50:903–906. doi: 10.1093/jac/dkf221. [PubMed] [Cross Ref]
4. Rasheed A, Ravichandran V, Kohli DV. Ampicillin prodrugs: amide conjugates from amino acids, peptide and ampicillin. Pharmazie. 1999;54:857–858. [PubMed]
5. Mandell GL, Douglas RG, Bennett JE, editors. Principles and Practice of Infectious Diseases. 3rd ed. New York, NY: Churchill Livingstone; 1990. pp. 240–242.
6. Acred P, Brown DM, Turner DH, Wilson MJ. Pharmacology and chemotherapy of ampicillin—a new broad-spectrum penicillin. Br J Pharmacol Chemother. 1962;18:356–369. [PubMed]
7. Harmoinen J, Vaali K, Koski P, et al. Enzymatic degradation of a beta-lactam antibiotic, ampicillin, in the gut: a novel treatment modality. J Antimicrob Chemother. 2003;51:361–365. doi: 10.1093/jac/dkg095. [PubMed] [Cross Ref]
8. Renke HG, Roos PC, Wells SG. Drug-induced interstitial nephritis with heavy glomerular proteinuria. N Engl J Med. 1980;302:691–692. [PubMed]
9. Linton AL, Clark WF, Driedger AA, Turnbull DI, Lindsay RM. Acute interstitial nephritis due to drugs. Review of the literature with the report of nine cases. Ann Intern Med. 1980;93:735–741. [PubMed]
10. Fontana G, Pitarresi G, Tomarchio V, Carlisi B, San Biagio PL. Preparation, characterization and in vitro antimicrobial activity of ampicillin-loaded polyethylcyanoacrylate nanoparticles. Biomaterials. 1998;19:1009–1017. doi: 10.1016/S0142-9612(97)00246-9. [PubMed] [Cross Ref]
11. Schumacher I, Margalit R. Liposome-encapsulated ampicillin: physiochemical and antibacterial properties. J Pharm Sci. 1997;86:635–641. doi: 10.1021/js9503690. [PubMed] [Cross Ref]
12. Peng L, Nimni ME. Delivery of erythromycin to subcutaneous tissues in rats by means of a trans-phase delivery system. J Pharm Pharmacol. 1999;51:1135–1141. doi: 10.1211/0022357991776822. [PubMed] [Cross Ref]
13. Martin RA. Anti-infective agents. In: Doerge F, editor. Wilson and Grisvold's Textbook of Organic Medicinal and Pharmaceutical Chemistry. 8th ed. Philadelphia, PA: JB Lippincott; 1991. pp. 129–187.
14. Siegel RA. Modeling of drug release from porous polymers. In: Rosoff M, editor. Controlled Release of Drugs, Polymers and Aggregate Systems. New York, NY: VcH Publishers; 1989. pp. 46–48.
15. Moffat AC, Osselton MD, Wildop B. Clarke's Isolation and Identification of Drugs. 2nd ed. London, UK: Pharmaceutical Press; 2004. pp. 635–635.
16. Rowe RC, Sheskey PJ, Weller PJ. Handbook of Pharmaceutical Excipients. 4th ed. London, UK: Royal Pharmaceutical Society of Great Britain; 2000. pp. 120–120.
17. Arora P, Mukherjee B. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt. J Pharm Sci. 2002;91:2076–2089. doi: 10.1002/jps.10200. [PubMed] [Cross Ref]
18. Baumgartner S, Kristl J, Peppas NA. Network structure of cellulose ethers used in pharmaceutical applications during swelling and at equilibrium. Pharm Res. 2002;19:1084–1090. doi: 10.1023/A:1019891105250. [PubMed] [Cross Ref]
19. Vlasses PH, Ribero LGT, Rotmensch HH, et al. Initial evaluation of transdermal timolol serum concentrations and β-blockade. J Cardiovasc Pharmacol. 1985;7:245–250. doi: 10.1097/00005344-198503000-00006. [PubMed] [Cross Ref]
20. Luo W, Catharina A, Harold CT. Rapid method for the determination of ampicillin residues in animal muscle tissue by high-performance liquid chromatography with fluorescence detection. J Chromatogr. 1997;694:401–407. doi: 10.1016/S0378-4347(97)00171-0. [PubMed] [Cross Ref]
21. Mehdizadeh A, Toliate T, Rouini RM, Abashzadeh S, Dorkoosh F. Design and in vitro evaluation of new drug-in-adhesive formulations of fentanyl transdermal patches. Acta Pharm. 2004;54:301–317. [PubMed]
22. Fang JY, Sung KC, Lin HH, Fomg CL. Transdermal iontophoretic delivery of diclofenac sodium from various polymer formulations: in vitro and in vivo studies. Int J Pharm. 1999;178:83–92. doi: 10.1016/S0378-5173(98)00361-5. [PubMed] [Cross Ref]
23. Krishnaiah YSR, Bhaskar P, Satyanarayana V. Formulation and evaluation of limonene-based membrane-moderated transdermal therapeutic system of nimodipine. Drug Deliv. 2004;11:1–9. doi: 10.1080/10717540490280372. [PubMed] [Cross Ref]
24. USP.US Pharmaceutical National Formulary. vol. USP 27 NF 22. 22nd ed. Rockville, MD: USP; 2003:140.
25. Sulochana KN, Bhooma V, Madhavan HN, Ramakrishnan S, Biswas A. HPLC method for simultaneous determination of ampicillin and sulbactam in biological samples glycerol. Int J Pharm. 1995;27:189–192.

Articles from AAPS PharmSciTech are provided here courtesy of American Association of Pharmaceutical Scientists