Formulation Development Of Florfenicol Oral Gel And Pharmacokinetic Study In Broiler

Florfenicol is a type of amide-alcohol antibiotic for animals that boasts a wide antibacterial spectrum and high safety.It has the ability to inhibit gram-negative and gram-positive bacteria as well as mycoplasma.Typically administered orally or via injection,florfenicol is used to prevent and treat bacterial infections in poultry such as chickens,pigs,fish,and other animals.Florfenicol is quickly absorbed and widely distributed throughout the animal’s body,and it demonstrates excellent antibacterial activity.Since its approval for clinical use in China,florfenicol has been recognized by veterinary professionals and farmers alike for its impressive efficacy,making it a promising candidate for broad market prospect.The oral preparation of florfenicol is convenient and economical,and is more suitable for the prevention and treatment of bacterial diseases in intensive rearing.However,the commonly used oral formulation of florfenicol-powder is usually administered by mixing with forage.After oral administration,the bioavailability in broilers is low,the mean residence time of effective blood drug concentration in vivo is short,and it is also easy to cause the problem of inaccurate dosage due to uneven mixing materials.Although some improvement can be made by making solid dispersions,slow and controlled release formulations,some drugs are still difficult to be absorbed and utilized due to the limitations of the dissolution and stability.Also,the development of most oral formulations is still in the basic research stage,and some new preparation technologies need to be invested at a high cost,which is not suitable for large-scale production of veterinary drugs.Therefore,the development of new oral formulations of florfenicol is of great significance.Gels offer a range of benefits,including improved drug dispersion,bioavailability,and targeted drug release in response to specific stimuli.As a result,they have become a focal point in the development of antibiotics,anti-tumor drugs,and other medications.The gel matrix is a crucial component for achieving formulation assignment,controlled release,and bioadhesion.Sodium alginate,a marine gel matrix,is a particularly attractive option due to its low cost,non-toxicity,biocompatibility,and renewable nature.Its mild gel condition allows it to rapidly form a low-viscosity and dispersed complex with calcium ions at room temperature,making it an ideal carrier for hydrophobic and hydrophilic drugs.This extends their retention time and improves their bioavailability.In addition,effective quality control is essential for ensuring the safety and efficacy of gels,and it is also important to establish a scientific and reasonable in vitro release evaluation method to predict the in vivo absorption of drugs more accurately.While numerous studies have detailed the principles and characteristics of different methods,further research is needed to determine the most appropriate physiological experimental conditions and to optimize the use of experimental techniques.Based on this,a gel matrix of sodium alginate and an ion cross-linker of calcium ions were utilized to design and prepare an oral gel containing florfenicol and its quality was evaluated.The study investigated its drug release under various methods and conditions through in vitro experiments,established a scientific and rational evaluation method.The pharmacokinetics and bioavailability of the oral gel were investigated through animal experiments,and the in vivo and in vitro correlation of the gel was investigated.The research content of this paper is divided into the following three sections:The first part of the study focused on the formulation of florfenicol oral gel.Sodium alginate with optimal viscosity and calcium ions were first selected based on gel morphology,with the results indicating that sodium alginate with a viscosity 150 mPa·s and calcium hydrogen phosphate were the best combination.Compatibility tests were then conducted on the raw materials and excipients to ensure that there were no adverse interactions between them.The results showed that the components had good compatibility.Furthermore,the gel formulation was screened and optimized using a single-factor test and a response surface method based on gel time and viscosity.The final formulation was composed of 10% florfenicol,3% sodium alginate,3% calcium hydrogen phosphate,84% starch,and a volume of water that was 10 times the mass of the powder.The results demonstrated that the oral gel produced was white,had a uniform texture,a gel time of 4.7 min,and a viscosity of 3510 mPa·s.Florfenicol oral gel exists in the form of powder in production,transportation,storage and sales.When it is used temporarily,water is added to make semi-solid gel.Its preparation process is simple,convenient for storage and transportation,and has good application value.The second part is the quality evaluation and characterization of florfenicol oral gel.The pH value,character stability,and content uniformity of the gel were assessed.Results showed that the pH value of the gel was 7.42,meeting the standards for oral administration.The gel demonstrated stability in centrifugal settings and content uniformity met the pharmacopoeia requirements.A rheometer,scanning electron microscope,X-ray diffractometer,and differential scanning calorimetry were used to analyze the gel’s characteristics.Results showed that the gel was predominantly composed of elastic components and its structure remained stable at low oscillation frequencies.SEM results indicated that sodium alginate and calcium hydrogen phosphate formed a gel with distributed florfenicol and starch within the gel frame.XRD and DSC results showed that florfenicol retained its original crystalline properties within the gel system and did not interact with other excipients.The in vitro drug release of the gel was then investigated under different gel forms,different pH values of the release medium,and various determination methods.Results showed that the in vitro release of gel was not significantly different when measured by different methods,but the pH of the release medium and the geometry had a greater impact.Finally,the pH 6.80 phosphate buffer was chosen as the release medium,and the basket method was preferred for testing the in vitro release of the complete gel.The third part of the study focused on the pharmacokinetics of florfenicol oral gel in rats and broilers.Initially,methods were developed to determine the concentration of florfenicol in plasma samples from both animals,and it was confirmed that these methods met the necessary detection requirements.Subsequently,the pharmacokinetic profile and bioavailability of gel after administration of florfenicol at a dose of 30mg/kg were investigated.The results indicated that the peak concentration of florfenicol in plasma was higher and the mean retention time was longer with the oral gel compared to the florfenicol powder in both rats and broilers.In rats,the absolute bioavailability of the gel was 79.16%,and the relative bioavailability was 165.5%.Similarly,the relative bioavailability of the gel in broilers was 179.3%,which demonstrated a significant improvement in the oral bioavailability of florfenicol in rats and broilers after the preparation of gel.Finally,the study explored the in vivo and in vitro correlation of the oral gel.The in vitro release rate(Fd)and in vivo absorption fraction(Fa)of florfenicol were curve-fitted at various time points(0.25,0.50,0.75,1.00,and 2.00 h),and the results showed a good linear relationship between the two,suggesting that the in vivo and in vitro correlation of the oral gel were closely correlated.In summary,a florfenicol oral gel with excellent performance was designed and prepared in this paper,a scientific and reasonable method for evaluating its drug release in vitro has been established,and a good in vitro and in vivo correlation has been established by in vitro release data and in vivo absorption data.The gel can greatly improve the oral bioavailability of florfenicol in rats and broilers and extend its action time in vivo,which is clinically significant.