Ciprofloxacin Formulations Research Articles

Removal of Ciprofloxacin and Norfloxacin from Aqueous Solution with Activated Carbon from Cupuaçu (Theobroma grandiflorum) Bark.

The widespread use of antibiotics such as fluoroquinolones (FQs) has raised environmental and health concerns. This study is innovative as we investigate the removal of ciprofloxacin (CIP) and norfloxacin (NOR) from water using activated carbon derived from cupuaçu bark (CAC). This previously discarded biomass is now a low-cost raw material for the production of activated carbon, boosting the local economy. CAC was physiochemically characterized, and adsorption experiments were designed using the Box-Behnken design to assess the effects of contact time, adsorbate concentration, and adsorbent dosage on the removal efficiency and adsorption capacity. The optimal conditions were determined using the desirability function, and kinetic, isothermal, and thermodynamic experiments were performed. CAC showed a 50.22% yield, low humidity (4.81%), and low ash content (4.27%), with acidic functional groups dominating. The surface area was 1335.66 m2/g, with an average pore volume of 0.753 cm3/g and a pore diameter of 2.206 nm. Adsorption was most effective at pH 5.0 due to electrostatic interactions between the basic adsorbent and cationic forms of CIP and NOR. Optimal conditions yielded adsorption capacities of 6.02 mg/g for CIP and 5.70 mg/g for NOR, with the Langmuir model suggesting monolayer adsorption. The regeneration with NaOH was effective, but the adsorption efficiency decreased below 50% after two cycles. These findings demonstrate that CAC is a sustainable, low-cost adsorbent for treating antibiotic-contaminated water.

Chitosan-Coated Liposome Formulations for Encapsulation of Ciprofloxacin and Etoposide.

Cancer and bacterial infections rank among the most significant global health threats. accounting for roughly 25 million fatalities each year. This statistic underscores the urgent necessity for developing novel drugs, enhancing current treatments, and implementing systems that boost their bioavailability to achieve superior therapeutic outcomes. Liposomes have been recognised as effective carriers; nonetheless, they encounter issues with long-term stability and structural integrity, which limit their pharmaceutical applicability. Chitosomes (chitosan-coated liposomes) are generally a good alternative to solve these issues. This research aims to demonstrate the effective individual encapsulation of ciprofloxacin (antibacterial, hydrophilic) and etoposide (anticancer, hydrophobic), within chitosomes to create more effective drug delivery systems (oral administration for ciprofloxacin, parenteral administration for etoposide). Thus, liposomes and chitosomes were prepared using the thin-film hydration technique and were characterised through ATR-FTIR, Dynamic Light Scattering (DLS), zeta potential, and release profiling. In both cases, the application of chitosomes enhanced long-term stability in size and surface charge. Chitosome-encapsulated ciprofloxacin formulations exhibited a slower and sustained release profile, while the combined effect of etoposide and chitosan showed heightened efficacy against the glioblastoma cell line U373. Therefore, coating liposomes with chitosan improved the encapsulation system's properties, resulting in a promising method for drug delivery.

Evaluation of the Activities of Commonly Dispensed Antibiotics at Bayero University Kano Health Care Services Unit

There is a growing concern about the effectiveness of antimicrobials in developing countries. Multifaceted factors contribute to the escalation of antibiotic resistance. The counterfeiting of antibiotic drugs is one facet of this. Antibiotics are the most counterfeited medicines worldwide. However, the WHO Committee for the review of Medicines accentuates surveillance checks even after the marketing of drugs or at the dispensing point. This study evaluated the activities of commonly dispensed antibiotics at Bayero University Kano health care service pharmacy unit. Fourteen brands of different antibiotics with the active ingredients amoxicillin, azithromycin, cefixime, ceftriaxone, ofloxacin, ciprofloxacin, and doxycycline were used. The antibiotic susceptibility testing was carried out using the Kirby Bauer disc diffusion method on clinical isolates of Escherichia coli, Staphylococcus aureus and Klebsiella pneumoniae. Typed strains of E. coli (ATCC 25923) and S. aureus (ATCC 25922) were also tested. Ciprofloxacin and ofloxacin-containing formulations had efficacy against all the clinical isolates and typed organisms. All organisms except K. pneumoniae were sensitive to azithromycin. Ceftriaxone was active only against E. coli (both clinical isolate and typed organism). About 71% of the antibiotics tested were not sensitive to the tested organisms. The inactivity observed may be due to the counterfeit or substandard nature of the antibiotics, ineffective storage, or the development of resistance. This necessitates more research to determine the extent of the problem and its causes at a large scale.

Quality Assessment of Selected Essential Antimicrobial Drugs from Drug Retail Outlets of Selected Cities in Eastern Ethiopia.

The prevalence of substandard and falsified (SF) antimicrobial drugs is increasing around the globe. This poses a great concern for the healthcare system. The consumption of SF antimicrobial drugs has the potential to result in treatment failure, emergence and development of antimicrobial resistance, and ultimately a rise in mortality rate. The objective of this study was to assess the quality of four commonly used antimicrobials marketed in the cities of Dire Dawa and Jijiga and the town of Togo-Wuchale, which have high potential for illegal drug trade activities in Ethiopia because they are located near the border with Somalia. A total of 54 brands/samples of amoxicillin, amoxicillin/clavulanic acid, ciprofloxacin, and norfloxacin formulations were collected covertly from 43 facilities using a convenience sampling strategy from March 16 to March 29, 2022. The samples were first screened using Global Pharma Health Fund (GPHF)-Minilab protocols and then analyzed using U.S. Pharmacopoeial and British Pharmacopoeia official methods. The quality evaluation detected no falsified product; however, it showed that 14.3% of the samples failed the GPHF-Minilab screening test semiquantitatively. Overall, 22.2% of the products analyzed did not meet any of pharmacopoeial specifications assessed: 13%, 12.2%, and 11.1% of the products failed in assay, dissolution, and weight variation, respectively. Additionally, 56.3% of amoxicillin samples, 60% of amoxicillin/clavulanate, 20% of ciprofloxacin, and 54.5% of norfloxacin samples were found to be pharmaceutically nonequivalent with their respective comparator products regarding dissolution profiles. The study showed the presence of substandard antimicrobial medicines in the eastern Ethiopian market.

Formulation and Evaluation of Ciprofloxacin Loaded Ocular Insitu Gel

Formulation and Evaluation of Ciprofloxacin Loaded Ocular Insitu Gel

Formulation and Evaluation of Ciprofloxacin, Miconazole, and Fluocinolone Acetonide Nanotechnology Based Ointment for Topical Drug Delivery System

Nanotechnology is a multidisciplinary field of science and engineering that deals with the manipulation and application of materials and structures at the nanoscale, typically involving objects with dimensions less than 100 nanometers. This emerging technology has revolutionized various industries, from electronics and medicine to materials science and energy production, by enabling scientists and engineers to work at the molecular and atomic levels.This research fully focused on the nanotechnology based drug delivery system.

In Vitro and In Vivo Evaluation of Inhalable Ciprofloxacin Sustained Release Formulations.

Respiratory antibiotics delivery has been appreciated for its high local concentration at the infection sites. Certain formulation strategies are required to improve pulmonary drug exposure and to achieve effective antimicrobial activity, especially for highly permeable antibiotics. This study aimed to investigate lung exposure to various inhalable ciprofloxacin (CIP) formulations with different drug release rates in a rat model. Four formulations were prepared, i.e., CIP-loaded PLGA micro-particles (CHPM), CIP microcrystalline dry powder (CMDP), CIP nanocrystalline dry powder (CNDP), and CIP spray-dried powder (CHDP), which served as a reference. The physicochemical properties, drug dissolution rate, and aerosolization performance of these powders were characterized in vitro. Pharmacokinetic profiles were evaluated in rats. All formulations were suitable for inhalation (mass median aerodynamic diameter < 5 µm). CIP in CHPM and CHDP was amorphous, whereas the drug in CMDP and CNDP remained predominantly crystalline. CHDP exhibited the fastest drug release rate, while CMDP and CNDP exhibited much slower drug release. In addition, CMDP and CNDP exhibited significantly higher in vivo lung exposure to CIP compared with CHDP and CHPM. This study suggests that lung exposure to inhaled drugs with high permeability is governed by drug release rate, implying that lung exposure of inhaled antibiotics could be improved by a sustained-release formulation strategy.

A model for analysis of antibiotic usage in low-income settings.

Quantification of antibiotic usage is an important component of antimicrobial stewardship programmes. We aimed to estimate institutional antibiotic usage and costs using methodology and metrics applicable to low-income settings without electronic health records. The DDD per 100 patient-days (DDDs/100 PDs) of antibiotics used in a calendar year was calculated retrospectively from ward registers and inpatient drug records in general surgical wards of a tertiary hospital. The antibiotics were categorized using the Access, Watch, Reserve classification. The annual expenditure on antibiotics was estimated from price lists of the state medication procurer. Annual usage of IV co-amoxiclav, cefuroxime and metronidazole was significantly higher than other antibiotics and certain wards showed outlier use of the same. The IV formulations of co-amoxiclav (5-fold), metronidazole (3-fold) and ciprofloxacin (2-fold) were used in excess of the oral formulation. Proportionate antibiotic usage based on the AWaRe category did not vary significantly between wards. Two wards were outliers for annual expenditure/100 PDs. IV clindamycin and meropenem combined accounted for 43.8% of expenditure on antibiotics. This study demonstrated intra-institutional variations of annual antibiotic usage and related costs. The metric DDD/100 PDs and the methodology used here are suitable for intra- and inter-institutional analyses of antibiotic usage, particularly in low-income settings.

New electrochemical reactor design for emergent pollutants removal by electrochemical oxidation

This paper presents the theoretical and experimental confirmation of the performance of a novel pre-pilot reactor design implementing a boron-doped diamond (BDD) anode to destroy emerging pollutants by electrochemical oxidation. Turbulent flow simulation and secondary current distribution modeling with a COMSOL Multiphysics software were used to assess the engineering capabilities of the reactor along with the oxidant BDD(·OH) electrogeneration at the anode. The antibiotic ciprofloxacin (CIP) was chosen as model molecule to assess the oxidation power achieved with the pre-pilot batch plant. In sulfate medium where BDD(·OH) was the main oxidant, faster degradation was determined by increasing current density, CIP content, and pH. The effect of pH was explained by the transformation of the cationic form of CIP in acidic medium into its more easily oxidizable anionic form in alkaline medium. In chloride medium, CIP was more rapidly removed by the faster attack of the generated active chlorine. The degradation was decelerated in carbonate medium by its scavenging effect and in the presence of humic acid by its competitive oxidation with BDD(·OH). The antibiotic abatement also dropped down in tap water and synthetic urine. An almost total mineralization was achieved with a constant energy cost per unit COD mass of 0.6 ± 0.1 kWh (g COD)−1. The initial N of CIP was pre-eminently converted into nitrate, alongside nitrite and ammonia to lesser extent. Recalcitrant acetic, oxalic, and formic acids were detected as final carboxylic acids.

Microfluidics assembly of inhalable liposomal ciprofloxacin characterised by an innovative in vitro pulmonary model

Respiratory tract infections (RTIs) are reported to be the leading cause of death worldwide. Delivery of liposomal antibiotic nano-systems via the inhalation route has drawn significant interest in RTIs treatment as it can directly target the site of infection and reduces the risk of systemic exposure and side effects. Moreover, this formulation system can improve pharmacokinetics and biodistribution and enhance the activity against intracellular pathogens. Microfluidics is an innovative manufacturing technology that can produce nanomedicines in a homogenous and scalable way. The objective of this study was to evaluate the antibiofilm efficacy of two liposomal ciprofloxacin formulations with different vesicle sizes manufactured by using a 3D-printed microfluidic chip. Each formulation was characterised in terms of size, polydispersity index, charge and encapsulation. Moreover, the aerosolisation characteristics of the liposomal formulations were investigated and compared with free ciprofloxacin solution using laser diffraction and cascade impaction methods. The in vitro drug release was tested using the dialysis bag method. Furthermore, the drug transport and drug release studies were conducted using the alveolar epithelial H441 cell line integrated next-generation impactor in vitro model. Finally, the biofilm eradication efficacy was evaluated using a dual-chamber microfluidic in vitro model. Results showed that both liposomal-loaded ciprofloxacin formulations and free ciprofloxacin solution had comparable aerosolisation characteristics and biofilm-killing efficacy. The liposomal ciprofloxacin formulation of smaller vesicle size showed significantly slower drug release in the dialysis bag technique compared to the free ciprofloxacin solution. Interestingly, liposomal ciprofloxacin formulations successfully controlled the release of the drug in the epithelial cell model and showed different drug transport profiles on H441 cell lines compared to the free ciprofloxacin solution, supporting the potential for inhaled liposomal ciprofloxacin to provide a promising treatment for respiratory infections.

Ciprofloxacin-loaded dissolving polymeric microneedles as a potential therapeutic for the treatment of S. aureus skin infections.

Microneedles have been widely studied for many topical and transdermal therapeutics due to their ability to painlessly puncture the skin, thereby bypassing the stratum corneum, the main skin barrier. In this study, ciprofloxacin (CIP) was loaded into dissolving polymeric microneedles prepared by a two-layer centrifugation method as a potential treatment of skin infections such as cellulitis. The polymers used were polyvinyl alcohol (PVA) and polyvinylpyrrolidone (PVP). Two formulations were investigated, namely CIP_MN1, composed of 10 mg ciprofloxacin incorporated into a polymer matrix of PVA and PVP with a weight ratio of (9:1), and CIP_MN2, composed of 10 mg ciprofloxacin incorporated into PVA polymer. CIP_MN1 and CIP_MN2 showed a mean microneedle height of 188 and 179 µm, respectively. Since Parafilm has been proven as a model to examine the perforation of microneedles in skin, it was used to evaluate the ability of microneedles to perforate the skin. CIP_MN1 showed almost complete perforation of Parafilm, 190 pores, compared to CIP_MN2 which created only 85 pores in Parafilm, and therefore CIP_MN1 was used for subsequent studies. Examining CIP_MN1 on agarose gel as an in vitro model of human skin showed that the formula was able to fully perforate the agarose gel. Moreover, this formula showed significantly greater antimicrobial activity (p < 0.0001) compared to a free gel of ciprofloxacin against Staphylococcus aureus in an agarose gel-based model. This was evidenced by a zone of inhibition of 29 mm for the microneedle formulation of ciprofloxacin (CIP_MN1) compared to 2 mm for the free gel of ciprofloxacin. Furthermore, the CIP_MN1 showed complete dissolution in human skin after 60 min from application. Finally, the skin deposition of CIP_MN1 was investigated in ex vivo excised human skin. CIP_MN1 showed significantly more deposition of ciprofloxacin in deeper skin layers compared to the free gel of ciprofloxacin, and the released ciprofloxacin from the microneedles tends to migrate to deeper layers with time. Collectively, these results suggest that CIP_MN1 can be a potential delivery system for the treatment of S. aureus skin infections.

A dual action of D-amino acids on anti-biofilm activity and moisture-protection of inhalable ciprofloxacin powders

Although inhalation powder aerosols of antibiotics have been used to treat respiratory infections caused by Pseudomonas aeruginosa, biofilms are difficult to clear. Ciprofloxacin and D-amino acids (D-Met, D-Trp and D-Phe) were shown to facilitate P. aeruginosa biofilm removal. Spray dried powders for inhalation tend to be amorphous, hence unstable to moisture which causes deterioration in the aerosol performance. Hydrophobic L-amino acids such as leucine can impart moisture protection. In this study, we hypothesized that co-spray dried formulations of ciprofloxacin and hydrophobic D-amino acids will offer the combined benefits of both anti-biofilm and moisture protection properties. Of the three D-amino acids tested, D-Met and D-Trp (at 5 mM) but not D-Phe reduced clinical isolate P. aeruginosa biofilm loads and the extent of biofilm clearance was further enhanced in the presence of ciprofloxacin. Subsequently, ciprofloxacin was spray dried alone or in combination with 30% (w/w) D-Met or D-Trp. The biological and physicochemical properties of the powders were assessed, including the minimum inhibitory concentration, anti-biofilm activity, particle size distribution and morphology, solid-state properties, water sorption, and aerosol performance. The spray dried combination powders were physically stable and inhalable with fine particle fraction (<5 µm) values of 50–57% when aerosolized. The powders exhibited enhanced anti-biofilm activity compared with ciprofloxacin alone. The presence of D-amino acids provided moisture protection, with the recrystallization event shifting from 50% RH to 80% RH in powders containing D-Trp. In conclusion, the use of D-amino acids (D-Met or D-Trp) is an attractive formulation strategy which offers dual benefits of anti-biofilm effect and moisture protection.

In Vitro Biopharmaceutical and Physicochemical Evaluation of Different Brands of Ciprofloxacin Marketed in Aden-Yemen

The current study conducted to evaluate the biopharmaceutical and physicochemical equivalence of the three available pharmaceutical dosage forms of ciprofloxacin (CIP) in the local markets (tablets, infusion and eye drops). Three brands for each dosage form were selected and coded as Tablets I, II, III; CIP infusion (Infusion I, II, III) and CIP eye drops (Eye drops I, II, III). Different in vitro quality control tests, physiochemical and determination of active ingredients contents were performed. All brands of tablets have a satisfactory result that complies with the pharmacopeia specification except the hardness of the tablets was more than the recommended value, and the salinity of Infusion II and III was lower than 0.9, the viscosity of the eye drops was lower than the specified value. Post-marketing surveillance is an essential issue to distinguish poor-quality medicines and must be routinely performed to weed out substandard and counterfeit medicine.

Geographic Variations in Pharmacy Services and Availability of Commonly Prescribed Pediatric Urology Medications: An Opportunity to Improve Health Equity in Washington State

To describe geographic and sociodemographic variations in operating hours and availability of medications commonly prescribed by pediatric urologists at Washington State retail pharmacies. We identified all retail pharmacies in the state. We stratified counties by population density and household income (HI) and compared differences in pharmacy operating hours and availability of 10 commonly prescribed medications. 1057/1058 pharmacies were contacted. All pharmacies had liquid formulations of oxycodone, hydrocodone, ibuprofen, acetaminophen, amoxicillin, and trimethoprim-sulfamethoxazole in stock. Liquid formulations of ciprofloxacin (10%) and oxybutynin (14.3%) were uncommonly stocked, while 92.5% of pharmacies stocked nitrofurantoin suspension, and 80.9% nitrofurantoin capsules. Statewide, 108 (10.2%) of pharmacies were closed on Saturdays and 297 (28.1%) closed on Sunday. More high (HPDC) than low population density (LPDC) (62.5% vs 0%, P < .001) and high-HI than low-HI counties (62.5% vs 0%, P=.30) had 24-hour pharmacies. A larger proportion of pharmacies were open 7-days in HPDC than LPDC (75.6% vs 56.2%, P < .0001) and in high-HI than low-HI counties (100% vs 62.5%, P=.30). The likelihood of a pharmacy being open 7 days/week was significantly higher in HPDC (vs LPDC; OR=13.2, 95% CI: 4.39-39.7) and high-HI (vs low-HI; OR=4.98, 95% CI: 2.58-9.60) counties. Most pharmacies in Washington State carry medications commonly prescribed by pediatric urologists. However, retail pharmacy operating hours are widely variable and create geographic and temporal barriers in rural and poor areas that may limit the timely administration of prescription medication. Providers should consider a patient's practical ability to fill a prescription when starting a time-sensitive medication.

Aqueous oxidation degradation of ciprofloxacin involving hydroxyl and sulfate radicals: A computational investigation

Aqueous oxidative degradation mechanism of three forms of ciprofloxacin (CIP) involving hydroxyl (OH) and sulfate radicals (SO4−) was investigated by performing density functional theory (DFT) calculation at the M06-2X/6–311 + G(d,p) level. The computational results indicated that hydrogen abstraction (HA) pathways occurring on piperazine ring were the most favorable in all plausible parallel channels. Electron transfer (ET) reactions between CIP and OH (SO4−) were impossible to occur. HA reactivities correlated well with the involved CH bond lengths and atomic charges of the abstracted H atoms. Compared with OH, SO4− was a stronger oxidant in degrading CIP. Piperazine ring cleavage was the main pathway in the early stage of CIP degradation involving OH (SO4−). Dissolved oxygen in water and water molecules could play significant roles in the oxidative degradation of CIP.

Design and Evaluation of Novel Sustained-Release Floating Microspheres for Oral Delivery of Ciprofloxacin Hydrochloride

Background: Ciprofloxacin (CIP) is a broad-spectrum antibiotic, used to treat various bacterial infections. Administration of conventional oral dosage forms of CIP is associated with multiple challenges such as short residence time of the drug in the gastrointestinal tract which could reduce bioavailability and effectiveness of the drug. This study aimed to design and develop novel floating microspheres for the sustained release of CIP in the stomach over 24 hours after oral administration, besides evaluating the effect of different variables on the characteristics of developed microspheres. Methods: Microspheres were developed by the solvent-evaporation method utilizing cellulose acetate and polyvinyl alcohol, then characterized for physicochemical properties including bulk density, buoyancy, and entrapment efficacy. The drug-excipient compatibility was evaluated by Fourier-transform infrared spectroscopy and the Scanning electron microscopy was used to observe the morphology of microspheres. The effects of the drug to polymer ratio, polymer concentration, and the pace of stirring through the preparation process, on the size and release rate were also evaluated. Results: Morphology analysis indicated round-shape microspheres with a mean particle size between 66-344 µm. The polydispersity index of prepared formulations was determined to be in the range of 0.129 to 0.230. It was observed that at higher polymer concentrations the drug release rate from microspheres decreased while the mean particle size increased. Increasing the drug to polymer ratio and decreasing the stirring speed increased the mean particle size. All formulations showed more than 70% cumulative drug release in the prolonged period of 24 h while remaining buoyant in the meantime. The formulations followed Higuchi and Korsmeyer-Peppas kinetics and release the drug by diffusion mechanism. Conclusions: Based on the results obtained from in vitro release study besides floating properties the prepared microspheres could be considered suitable for enhanced sustained-release of CIP following the oral administration.

Use of Natural Clinoptilolite in the Preparation of an Efficient Adsorbent for Ciprofloxacin Removal from Aqueous Media

The adsorption of the antibiotic ciprofloxacin (CIP) from an aqueous solution by natural zeolite, the calcium-rich clinoptilolite (CLI), and magnetite-coated CLI (MAG-CLI) was investigated. Both CLI and MAG-CLI showed a high adsorption affinity towards CIP at 283, 288 and 293 K at a pH of 5. Adsorption kinetics studied for the initial concentrations of 15–75 mg CIP dm−3 follow Lagergren’s pseudo-second order equation and the adsorption is best represented by the Langmuir model. The adsorption mechanism involves strong electrostatic interactions between negatively charged aluminosilicate lattice and the cationic form of CIP accompanied by an ion-exchange reaction. Magnetite coverage (approx. 12 wt.%) induces magnetism, which can facilitate the separation process. The coverage does not influence the adsorption activity of CLI. The leaching test showed that the MAG coating protects the adsorbent from CIP leaching. This is ascribed to interactions between the CIP carboxyl groups and magnetite nano-particles. Antibacterial tests showed strong antibacterial activity of the ciprofloxacin-containing adsorbents towards pathogenic E. coli and S. aureus.

Microbiological justification of the application of cyprofloxacin and tinidazole combination for antimicrobial chemistry in dentistry

Relevance. According to modern concepts, virulent representatives of periodontal pathogenic bacteria are actively involved in the development of both periodontal pathology and various forms of odontogenic infection. The species diversity of these pathogens determines the need for a combined approach when choosing antimicrobial drugs.The aim of the work is to provide a microbiological substantiation of the use of a combined dosage form of ciprofloxacin and tinidazole for the treatment of periodontal and odontogenic infections based on the determination of the spectrum of action and the characteristics of the activity of the components.Materials and methods. Determination of the sensitivity of various strains of periodontal and odontogenic infection pathogens (P. intermedia, S. constellatus; S. sanguis, K. pneumoniae, S. aureus – MRSA) was carried out by the method of automated cultivation of strains with different concentrations of the tested drugs – ciprofloxacin and tinidazole.Results. Differences in the activity of the components of the combined preparation ciprofloxacin and tinidazole were found in terms of the sensitivity of strains of aerobic and anaerobic pathogens to them. Aerobic strains, including MRSA, were inhibited by ciprofloxacin in a low concentration range (6.25 μg / ml), but for some anaerobic strains the activity of ciprofloxacin was borderline (12.5 μg / ml). This confirmed the need to include tinidazole in the composition of the complex preparation.Conclusion. The combination of ciprofloxacin and tinidazole provides coverage of the full spectrum of periodontal and odontogenic infections and can be used as the agent of choice in the antimicrobial chemotherapy algorithm for head and neck infections.

Investigating the Impact of Crohn's Disease on the Bioaccessibility of a Lipid-Based Formulation with an In Vitro Dynamic Gastrointestinal Model.

The aim of the study was to investigate the impact of Crohn's disease (CD) on the performance of a lipid-based formulation of ciprofloxacin in a complex gastrointestinal simulator (TIM-1, TNO) and to compare the luminal environment in terms of bile salt and lipid composition in CD and healthy conditions. CD conditions were simulated in the TIM-1 system with a reduced concentration of porcine pancreatin and porcine bile. The bioaccessibility of ciprofloxacin was similar in simulated CD and healthy conditions considering its extent as well as its time course in the jejunum and ileum filtrate. Differences were observed in terms of the luminal concentration of triglycerides, monoglycerides, and fatty acids in the different TIM-1 compartments, indicating a reduction and delay in the lipolysis of formulation excipients in CD. The quantitative analysis of bile salts revealed higher concentrations for healthy conditions (standard TIM-1 fasted-state protocol) in the duodenum and jejunum TIM-1 compartments compared to published data in human intestinal fluids of healthy subjects. The reduced concentrations of bile salts in simulated CD conditions correspond to the levels observed in human intestinal fluids of healthy subjects in the fasted state.A lipidomics approach with ultra performance liquid chromatography (UPLC)/mass spectrometry (MS) has proven to be a time-efficient method to semiquantitatively analyze differences in fatty acid and bile salt levels between healthy and CD conditions. The dynamic luminal environment in CD and healthy conditions after administration of a lipid-based formulation can be simulated using the TIM-1 system. For ciprofloxacin, an altered luminal lipid composition had no impact on its performance indicating a low risk of altered performance in CD patients.

Storage stability of phage-ciprofloxacin combination powders against Pseudomonas aeruginosa respiratory infections.

Novel inhalable and synergistic combination powder formulations of phage PEV20 and ciprofloxacin were recently developed to treat Pseudomonas aeruginosa respiratory infections. In the present study, we investigated the storage stability of these powders which comprised ciprofloxacin, lactose and L-leucine in mass ratios of 1:1:1 (Formulation A) or ciprofloxacin and L-leucine in 2:1 without lactose (Formulation B). These powders were produced by spray drying, collected in polypropylene tubes and packed inside aluminium pouches which were heat-sealed at<20% relative humidity (RH), then stored at 4°C or 25°C. The phage viability, aerosol performance and solid-state properties of the powders were examined over 12months. The biological activity and aerosol performance of both formulations showed no significant change over 12months of storage at 4°C. However, after four months of storage at 25°C, a significant titer loss of 2.2 log10 (p<0.01) was observed in Formulation B, but the loss in Formulation A was much less (0.5 log10 (p<0.05)). In contrast, the fine particle fraction (FPF, wt. % particles≤5µm) of Formulation A was significantly reduced by 11% (p<0.05) after four months of storage at 25°C, whereas the aerosol performance of Formulation B remained stable over 12months. The results showed that ciprofloxacin can sufficiently stabilize phage through vitrification and/or hydrogen bonding at 4°C. The presence of lactose was beneficial to preserve the phage at 25°C. In conclusion, spray dried PEV20-ciprofloxacin combination powders were biologically and physico-chemically stable even without lactose as a stabilising excipient, when stored below 20% RH at 4°C for 12months.