Oral Suspension Formulation Research Articles

Analysis of amoxycillin in capsules and oral suspensions by high-performance liquid chromatography

A method has been developed for assay of amoxycillin (AMX) from pharmaceutical preparations which is an advance on previously published methods. It makes use of an isocratic HPLC system. The chromatographic conditions comprised a reversed-phase C18 column (100 mm × 2 mm) with a mobile phase of methanol–50 mmol l–1 aqueous phosphate buffer (3 + 97) at pH 7.0 pumped at 0.4 ml min–1. Ultraviolet detection was at 230 nm and a photodiode array detector was used for examination of peak homogeneity. The method involves a simple sample pre-treatment stage for capsules and oral suspension formulations and has been validated (for linearity, accuracy, precision and specificity) according to current guidelines. The two major starting materials used in the synthesis of AMX can be detected and the method has been shown to indicate stability. The method was used to assay AMX capsule and oral suspension samples from Nigeria and Thailand as part of a larger study investigating the quality of pharmaceuticals in developing countries. From these analyses sub-standard AMX preparations were found from both countries.

Stability of dantrolene oral suspension prepared from capsules.

The chemical stability of an extemporaneously compounded dantrolene oral suspension (5 mg/ml dantrolene sodium) in Syrup BP containing citric acid with and without methyl hydroxybenzoate preservative was studied on storage at 5, 25 and 40 degrees C for 150 days in high density polyethylene dispensing bottles. The amount of dantrolene free acid in suspension was monitored by a stability indicating HPLC assay. There was no significant decomposition of dantrolene under all storage conditions irrespective of the presence of preservative. The results show that the formulation of dantrolene oral suspension provides a convenient and stable dosage form for use in pediatric patients and in those unable to swallow capsules. It is recommended that the formulation be stored at room temperature and in the absence of microbiological testing a shelf-life of 30 days is proposed for the product prepared with preserved syrup.

Safety profile of cefixime: Results of a german postmarketing surveillance study of 6361 patients

The safety profile of cefixime was evaluated in 6361 adult and pediatric patients with mostly respiratory tract infections; urinary tract infections; and ear, nose, and throat infections. The daily dose of cefixime was 400 mg in adults and 8 mg/kg body weight in children. Cefixime was administered once daily in 62.4% of patients and twice daily in 36.3% of patients. In 57 patients (0.9%) the dosage regimen changed during therapy and in 28 patients (0.4%) no information on dosage was available. Cefixime was administered as tablets or suspension. Adverse events were experienced in 493 (7.8%) of 6361 patients; 477 of the 610 adverse events were gastrointestinal in nature. In 236 (7.4%) of the 3194 patients treated with tablets, 309 adverse events were reported, compared with 295 adverse events in 253 (8.06%) of 3138 patients treated with oral suspension form. Of the 610 adverse events reported, 292 (47.9%) were classified as at least moderately severe and at least possibly related to cefixime. Seventy-three (12.0%) of the reported adverse events were assessed as severe. Thirty-three patients discontinued the study prematurely. Once-daily administration of cefixime was at least safe as twice-daily administration. The results of this postmarketing surveillance study demonstrate that cefixime is well tolerated in daily practice.

Clarithromycin and cefaclor suspensions in the treatment of acute otitis media in children

The safety and efficacy of a new oral suspension formulation of clarithromycin were evaluated in this multicenter, Phase III, single blind, comparative trial in 379 children ages 6 months to 12 years with signs or symptoms of acute otitis media. Children were randomized to receive a 10-day course of clarithromycin oral suspension (7.5 mg/kg; maximum, 500 mg) or cefaclor oral suspension (20 mg/kg; maximum, 500 mg) twice daily. Specific clinical response criteria were developed based on pretreatment signs and symptoms and results of tympanometry. Of the 379 enrolled patients 281 (74%) were evaluable (clarithromycin, 150; cefaclor, 131). There were no demographic differences between the two groups. Fifty percent of the patients had 2 to 4 episodes of otitis media (including the current episode) in the past 12 months; 63% of the patients had an infection of moderate severity. Clarithromycin and cefaclor suspensions were similarly effective for the treatment of acute otitis media. Clinical success (cure, cure with effusion or improvement) was achieved in 86% of clarithromycin-treated patients and 90% of cefaclor-treated patients. The majority of bacterial isolates for which susceptibility results were available were fully or moderately susceptible to the study drugs (96% clarithromycin, 92% cefaclor). Both drugs were well-tolerated; adverse events considered probably study drug-related were reported by 30 (15%) of clarithromycin recipients and 31 (17%) of cefaclor recipients. There were no significant differences between the groups in the numbers of patients reporting events that were thought to be related to study medication.(ABSTRACT TRUNCATED AT 250 WORDS)

A kinetic study of metronidazole benzoate hydrolysis by reverse-phase high performance liquid chromatography

Metronidazole benzoate (I) is a white powder used in oral suspension formulations because it is much less bitter than metronidazole (II). In suspension formulation, I may hydrolyze to II, leading to an unacceptable and bitter suspension. The kinetics of hydrolysis of the ester were investigated at several temperatures as a function of pH in aqueous solutions. The reaction was followed by measuring the decrease in the concentration of I and/or the increase in the concentration of II as a function of time using the reverse phase HPLC method. The pH rate profile was determined between pH 0 and 10. Hydrolysis at pH 11 was almost instantaneous at 25 °C. The hydrolysis was shown to be pseudo-first order with respect to I. The reaction rate constant at pH 10 was three orders of magnitude larger than that at pH 6. The hydrolysis products, namely, metronidazole (II) and benzoic acid (III,) were identified by HPLC using C 18 column and detector wavelengths at 270 and 320 nm. Arrhenius plots were obtained from which activation energies and shelf-lives were calculated.

Formulation of a Cimetidine Oral Suspension

Formulation of a Cimetidine Oral Suspension

Quantitative Determination of Cephalexin in Cephradine by NMR Spectroscopy

An NMR method to determine quantitatively the presence of cephalexin in cephradine was developed. The method is applicable to the chemical itself as well as to capsules and oral suspension formulations. The determination is based on the NMR signal arising from the five aromatic protons of the cephalexin molecule. Integration of this signal relative to a signal from cephradine provides the data necessary to determine the percentage of cephalexin present. The precision at the 2% cephalexin level is ±0.18%. The time required to carry out a single analysis is about 10 min, and five analyses can be done in about 0.5hr.