Preparation And Pharmacokinetics Of Clarithromycin Microcapsules

In recent 40 years, microcapsules are a new drug delivery system, with natural or synthetic polymer materials as coating materials, which encapsulates solid or liquid drugs in. The size is generally from 10 to 1000μm. Compared with traditionary drug delivery systems, microcapsules have many advantages, such as covering up the bad smell or taste, increasing the stability of drugs, preparing for sustained-release or controlled-release preparations etc.Clarithromycin is a semisynthetic macrolides antibiotic with a broad essentially bateriostatic action against many Gram-positive and some Gram-negative bacteria, as well as some anaerobes. It has been widely used clinically to treat respiratory tract infection, urogenifal infection, skin and soft tissue infection etc. Its side effect incidence is low. It is the principal drug for respiratory tract infection, especially for children.The dosage forms of Clarithromycin are simple. Above 60% of them are traditional tablets and capsules. Due to the shortcomings of the existing preparations of clarithromycin, such as low bioavailability, large administration dosage and incomplete absorption, its applications have been greatly limited.The objective of this thesis was to study the preparation, quality evaluation and in vivo behavior of microcapsules with clarithromycin as a model drug in details.There were five chapters in this thesis.Chapter one:A review was concerned with the application characteristics, the recent progress in microcapsules, the varieties of coating materials, the preparing methods, the factors of effecting particle size, release mechanism and quality evaluation. The research objective and significance on clarithromycin were introduced in brief.Chapter two:Developed a quantitative analysis method (HPLC) through preformulation. The analytical method was simple, with high sensitivity, specificity and recovery for the next studies of formulation and preparing technology.Chapter there:The impact factors of clarithromycin microcapsules on preparing technology were studied, such as the types and dosages of surface active agents, clarithromycin-EC ratio, stirring speed, temperature and oil-water ratio etc. We ultimately selected the suitable microencapsulated prescription and technology, and prepared ideal clarithromycin microcapsules. Chapter four: The quality evaluation of clarithromycin microcapsules was studied by apparatus in details, including morphology evaluation, particle size and distribution, drug loading rate and entrapment rate, the release behavior in vitro, stability, sensory test and finally a suitable preparation was selected for the next study etc.Chapter five:A simple and sensitive in vivo method of clarithromycin was developed. Clarithromycin commercial tablet as reference, pharmacokinetics of clarithromycin microcapsules in oral administration was studied primarily. Compared with the reference group, the microcapsules can improve the bioavailability, and mask the bitter taste of crude drug.