Ciprofloxacin formulations

Webb MS, Boman NL, Wiseman DJ, et al. Antibacterial efficacy against an in vivo Salmonella typhimurium infection model and pharmacokinetics of a liposomal ciprofloxacin formulation. Antimicrob Agents Chemother 1998 42 45. 

The complete degradation of sulfamethoxazole was also reported within 14 days with P. chrysosporium, Bjerkandera sp. R1 and B. adusta [4], although, contrary to the reports of enzymatic transformation, metabolites were not identified. Partial removal (from 30% to 55%) of sulfamethoxazole from activated-sludge-mixed liquor and the effluent of a WWTP was demonstrated at bench scale within 5 days with P. chrysosporium propagules entrapped in a granular bioplastic formulation [25]. This approach was also successful in the partial elimination of other kinds of antibiotics, eg., ciprofloxacin (see below) and the macrolide erythromycin. 

Hope MJ, Wong KF. Liposomal formulation of ciprofloxacin. In Shek PN, ed. Liposomes in Biomedical Applications. Harwood Academic Publishers, 1995 121. 

Proquin XR Proquin XR and other oral formulations of ciprofloxacin are not interchangeable. Proquin XR should be administered orally once daily for 3 days with a main meal of the day, preferably the evening meal. Proquin XR should be administered at least 4 hours before or 2 hours after antacids containing magnesium or aluminum, sucralfate, Videx (didanosine) chewable/buffered tablets or pediatric powder, metal cations such as iron, and multivitamin preparations containing zinc. Pragy/n XR tablets should be taken whole and never split, crushed, or chewed. 

The good bioavailability of orally administered ciprofloxacin obviates the need for the more expensive intravenous formulation. I.v. ciprofloxacin is only given to patients who have severe sepsis or severe nausea and vomiting. Ciprofloxacin s elimination is 50% hepatic and 50% renal. Therefore, dose reduction is recommended only in case creatinine clearance drops to < 10 ml/min. Prevention of food-borne disease requires efforts at many levels. Monitoring safety of food processing, vector control, surveillance of outbreaks, education on personal hygiene and improving sanitation and access to safe water supplies are all necessary measures to reduce the incidence of GTI. 

Sustained-release formulations can produce stable serum concentrations with once or twice daily dosage. Therapeutic effects occur at blood levels > 5 mg/1, and side effects increase considerably at levels > 15 mg/1. Smoking, alcohol, anticonvulsants, and rifampicin induce the drug-metabolizing enzyme system in liver and reduce the half-life of theophylline. On the other hand, heart and liver failure, sustained fever, old age and drugs such as cimeti-dine, ciprofloxacin, and oral contraceptives reduce theophylline clearance and thereby increase serum concentrations. 

Solutions of ciprofloxacin are light sensitive and should be protected from light and freezing [3]. When the concentrate formulated for intravenous injection, or the 1.2 g pharmacy bulk package, is diluted with 5% dextrose injection or 0.9% sodium chloride injection to a final concentration of 0.5-2 mg/mL, the resultant solution is stable for upto 14 days when stored at room temperature or when refrigerated at 2 8°C [5]. 

The commercially available injection for intravenous infusion that contains 2 mg/mL in 5% dextrose is provided in a plastic container fabricated from a specially formulated polyvinyl chloride (PVC). Tammilehto et al. used thin-layer chromatography to study the degradation of ciprofloxacin hydrochloride solutions after these were irradiated by a high pressure mercury lamp [6]. 

The assay of an IV formulation is performed using a liquid chromatographic method, which requires the following solutions. For solution (1), dilute a quantity of the intravenous infusion with sufficient mobile phase to produce a solution containing the equivalent of 0.05% w/v of ciprofloxacin. Solution (2) contains 0.058% w/v of ciprofloxacin hydrochloride EPCRS in mobile phase. Solution (3) contains 0.025% w/v of ciprofloxacin impurity C EPCRS (ethylenediamine compound) in solution (2). For solution (4), dilute 1 volume of solution (3) to 100 volumes with the mobile phase. The chromatographic procedure may be carried out using a stainless steel column (12.5 cm x 4 mm) packed with stationary phase C (5 mm) (Nucleosil C18 is suitable). The mobile phase is eluted at a flow rate of 1.5 mL/min, and consists of a mixture of 13 volumes of acetonitrile and 87 volumes of a 0.245% w/v solution of orthophosphoric acid (the pH of which has been adjusted to 3.0 with triethylamine). Analytes are detected on the basis of their UV absorption at 278 nm. The assay is not valid unless in the chromatogram obtained with solution (3), the resolution factor between the peaks due to ciprofloxacin and the ciprofloxacin impurity C is at least 1.5. 

Calculate the content of Ci7Hi8FN303 in the intravenous infusion formulation using the declared content of C17H19CIFN3O3 in ciprofloxacin hydrochloride EPCRS. Each milligram of Ci7H19ClFN303 is equivalent to 0.9010 mg of Ci7HigFN303. The ciprofloxacin content should be 95.0-105.0% of the label claim. 

Several methods were reported in the literature for the determination of ciprofloxacin in pharmaceutical formulations and in biological fluids. 

Rizk et al. developed a sensitive and selective derivative UV-spectrophotometric method for the determination of three fluoroquinolone compounds, including ciprofloxacin, in formulations and spiked biological fluids (7]. The method depends on the complexation of Cu(II) with the studied compounds in an aqueous medium. A linear correlation was established between the amplitude of the peak and the drug concentration over the range of 35-120 ng/mL. The detection limit was reported as 1.3 ng/mL. The method was used for the determination of the ciprofloxacin bulk drug substance and its tablet formulation, with an overall percentage recovery of 99.22 0.55 to 100.33 1.60. 

Amin described a simple and sensitive spectrophotometric method for the determination of three gyrase inhibitors, including ciprofloxacin, in pharmaceutical formulations [10]. This method is based on the formation of an ion pair with Sudan III in 40% v/ v aqueous acetone. The color of the dye changes at 566 nm in the presence of ciprofloxacin. Beer s law is obeyed over the range of 0.4-10.4 pg/mL, and the results showed good recovery (100 1.7%) with a RSD of 1.08%. 

Ciprofloxacin is commercially available as the monohydrate phase of its hydrochloride salt, and has been formulated for oral and ophthalmic administration. The compound has also been developed as the lactate salt for use in intravenous administration [3]. 

Nijhawan, R., and Agarwal, S. P. (2003), Development of an ophthalmic formulation containing ciprofloxacin-hydroxypropyl-P-cyclodextrin complex, Boll. Chim. Farm,., 142(5), 214-219. 

Charoo, N. A., Kohli, K., Ali, A., and Anwer, A. (2003), Ophthalmic delivery of ciprofloxacin hydrochloride from different polymer formulations In vitro and in vivo studies, Drug Dev. Ind. Pharm., 29(2), 215-221. 

Damle BD, Mummaneni V, Kaul S, Knupp C. Lack of effect of simultaneously administered didanosine encapsulated enteric bead formulation (Videx EC) on oral absorption of indinavir, ketoconazole, or ciprofloxacin. Antimicrob Agents Chemother 2002 46(2) 385-91. 

QUINOLONES DIDANOSINE 1 efficacy of ciprofloxacin and possibly levofloxacin, moxifloxacin, norfloxacin and ofloxacin with buffered didanosine Cations in the buffer of didanosine preparation chelate and adsorb ciprofloxacin. Absorption of the other quinolones may be i by the buffered didanosine formulation, which raises gastric pH Give the antibiotic 2 hours before or 6 hours after didanosine. Alternatively, consider using the enteric-coated formulation of didanosine, which does not have to be given separately... 

Magnesium trisilicate is used in oral pharmaceutical formulations and food products as a glidant. It is also used therapeutically as an antacid, and also for the treatment of ciprofloxacin overdose or toxicity. ... 

Ciprofloxacin (40mg/ml) is approved for i.v. administration to humans. Tliis formulation must be diluted and administered slowly and is extremely expensive. Enrofloxacin is available as an injectable solution (50 mg/ml) and tablets for p.o. administration to small animals and as a solution (lOOmg/ml) for s.c. administration to cattle. Both of these injectable solutions may be... 

As patients improve clinicaUy, the route of administration should be reevaluated. Streamlining therapy from parenteral to oral (switch therapy) has become an accepted practice for many infections outside the bloodstream and CNS. Criteria that should be present to justify a switch to oral therapy include (1) overall clinical improvement, (2) lack of fever for 24 to 48 hours, (3) decreased WBC count, and (4) a functioning gastrointestinal tract. Drugs that exhibit excellent oral bioavaUabifity when compared with intravenous formulations include ciprofloxacin, clindamycin, doxycycline, gatifloxacin, levofloxacin, metronidazole, moxifloxacin, linezolid, and trimethoprim-sulfamethoxazole. 

DETERMINATION OF CIPROFLOXACIN IN PHARMACEUTICAL FORMULATION BY CHEMILUMINESCENCE METHOD... 

Nagaralli B, Seetharamappa J, Melwanki M. Sensitive spectrophotometric methods for the determination of amoxycillin, ciprofloxacin and piroxicam in pure and pharmaceutical formulations. J Pharm Biomed Anal 2002 29 859-864. 

Husain, S. Khalid, S. Nagaraju, V. Rao, R.N. High-performance liquid chromatographic separation and determination of small amounts of process impurities of ciprofloxacin in bulk drugs and formulations. J.Chromatogr.A, 1995, 705, 380—384... 

An extremely marked reduction in the serum levels of ciprofloxacin occurs if it is given at the same time as didanosine tablets, because of an interaction with the antacid buffers in the didanosine formulation. Taking the ciprofloxacin 2 hours before or 6 hours after didanosine tablets minimises this interaction. Other quinolones are expected to interact similarly. Didanosine enteric-coated capsules do not interact with ciprofloxacin. 

When 12 healthy subjeets were given ciprofloxacin 750 mg with two didanosine plaeebo tablets (i.e. all of the antacid additives but no didanosine), the ciprofloxacin AUC and maximum serum levels were reduced by 98% and 93%, respectively. The antacids in this formulation were dihy-droxyaluminium sodium carbonate and magnesium hydroxide. 

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