Bioequivalence of Two Oral Extended Release Formulations of Ciprofloxacin Tablets in HealthyMale Volunteers under Fed and Fasting Conditions

Abstract

The bioavailability of a single dose of ciprofloxacin 1000 mg Extended release (XR) tablets manufactured by a Jordanian manufacturer (Hikma PLC), was compared with a reference ciprofloxacin 1000 mg XR tablets (Cipro® XR, Bayer-health care, Germany) in two different studies (under fasting and fed conditions). In each study, 28 healthy, male, Jordanian volunteers were enrolled. However, only 25 subjects in fasting study and 23 subjects in fed study completed the crossover. Each study was designed as single-center, open-label, randomized, singledose, two-way crossover study. Nineteen blood samples were taken during 24hrs. Samples were frozen and kept until time of analysis. Ciprofloxacin concentrations in subjects' plasma were determined by using a validated HPLC fluorescence technique. Confidence intervals (90%) for the peak plasma concentration (C max ) and area under the concentration-time curve (AUC0-t) were determined by calculating log-transformed Test/Reference ratio using standard non-compartmental method and ANOVA statistics. The 90% CI result in fasting study for C max was 88.87 (82.17 -96.10)% and for AUC0-t was 87.60 (80.38-95.46)%. In fed study the results were 102. 09 (92.77-112.34)% and 104.06 (100.01-108.27)% for Cmax and AUC0-t, respectively. In conclusion, it is evident that the 90% CI for the primary pharmacokinetics parameters was within the bioequivalence acceptable boundaries of 80-125%, while for AUC0-t, and 75.-133% for C max . Therefore, it was concluded that both products were bioequivalent.

The impact of food intake on the luminal environment and performance of oral drug products with a view to in vitro and in silico simulations: a PEARRL review

“…used TIM‐1 and tiny‐TIM to test poorly water‐soluble drugs (PWSDs) in various formulations [ciprofloxacin: BCS class IV, 500 mg IR tablet Ciprobay ® and film‐coated ER tablet Ciproxin ® ; posaconazole: BCS class II, 40 mg/ml IR suspension Noxafil ® ; nifedipine: BCS class II, 10 mg IR capsule Adalat ® and 60 mg ER tablet Adalat ® XL] under fasted and fed conditions. No food effect was observed on the maximum amount of bioaccessible ciprofloxacin during GI transit (BA max ) in line with the t max , C max and AUC reported for human studies . A large positive food effect was observed for posaconazole, with a 4‐ to 5‐fold increase in BA max , in line with the in vivo 4‐fold increase in C max and AUC .…”

Together or Apart? Revealing the Impact of Dietary Interventions on Bioavailability of Quinolones: A Systematic Review with Meta-analyses

“…Most food-effect studies for ciprofloxacin involved immediate-release (IR) tablet formulation, and results indicated decreased drug absorption. However, Omari et al tested two types of extended-release (ER) ciprofloxacin tablets (the marketed and experimental) and found no clinically significant changes in AUC and C max in fed versus fasted state [ 45 ]. Similarly, Shah et al revealed a slight, clinically irrelevant decrease in the rate of postprandial ciprofloxacin bioavailability when given as an oral suspension [ 46 ].…”

“…Lack of interaction with food makes both the ER tablet and the oral suspension of ciprofloxacin preferable formulations. Moreover, the ER formulation may provide better compliance and reduced frequency of gastrointestinal side effects compared to IR tablets [ 45 ], whereas the liquid form can be primarily used in the aging population and patients with swallowing difficulties.…”

Role of Pharmacokinetic Studies in Drug Discovery

“…The primary concern in pharmacokinetic studies is to limit the consumer's and manufacture's risk. This is done by using appropriate statistical methods for data analysis and adequate sample size [57]. In a study with a sufficient amount of data, mean values, variance, and confidence intervals of drug concentrations and pharmacokinetic parameters should be estimated using appropriate statistical methods [58][59][60].…”