Formulation and Characterization of Novel Pegylated Self nanoemulsifying Formulations (Snefs) For Oral Delivery of Gentamicin and Its Possible Use in the Treatment of Pneumococcal Meningitis.
ABSTRACT
The solubility of gentamicin in various formulation vehicles (oils, surfactants and co-surfactants) was determined using the shake flask method. Emulsifying ability of the surfactants for the selected oil was screened.
Different SNEF prototypes were developed following the construction of ternary phase diagrams using water titration method. The effect of drug and other additives on the ternary phase diagrams were studied and the selected formulations were optimized.
Optimized formulations were characterized by weight uniformity of their capsule shells and visual assessment of their self nanoemulsification. The optical clarity and robustness to dilution of the SNEFs were evaluated.
Emulsification time, droplet size, zeta potential, polydispersity index and Fourier transform-infrared spectroscopy were measured. SNEFs were also characterized by scanning electron microscopy (SEM).
Apparent viscosities, absolute drug content and drug content efficiencies were determined. Stability studies and octanol/water partition coefficient were evaluated, while in vitro antibacterial studies of the SNEFs and permeation studies were carried out.
In vitro anti-pneumococcal study of the SNEFs against S. pneumoniae was done followed by extrapolation of their minimum inhibitory concentrations (MICs).
INTRODUCTION
Over the past years, the fraction of new drug products that are new chemical entities has steadily decreased, reflecting the tremendous cost required to bring new drugs to the marketplace. Increased understanding of drug metabolic and toxicological factors, such as the effect of the patient age on drug distribution,
the genetic factors that may result in dramatic intersubject variability in metabolism, short term versus long-term exposure toxicities, and the potential for teratogenic, mutagenic and embryotoxic effects, has increased the scrutiny under which governmental agencies view the chemical entity.
This careful inspection is intended to minimize the possibility of toxic reaction(s) and to demonstrate the safety and efficacy of new drug products. The regulatory process has also resulted in significantly more costly and time-consuming testing prior to commercialization.
This increased emphasis on safety has placed an additional burden on those who are involved in the development of new drugs, while increasing financial pressures have led to the need for decreased development time.
The investigation of approved drugs has resulted in enhanced patient safety and therapeutic efficacy by directing research efforts toward the more efficacious delivery of known pharmacologically active agents to the appropriate physiologic site.
This trend has caused pharmaceutical researchers to seek the most suitable methods to deliver both new and existing compounds in the most pharmacologically appropriate manner. The methods may be designed to optimize bioavailability, minimize toxicity and side effects, and improve stability.
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