DEVELOPMENT AND EVALUATION OF LYOPHILIZED POWDER TO PREPARE SOLUTION FOR INJECTIONS BASED ON DOXYCYCLINE

The range of doxycycline drugs on the pharmaceutical market of the Ukraine is very limited and is represented by solid forms (capsules and tablets) while a rapid effect and maximum bioavailability of the drug can be provided by parenteral administration. The object of the study is the drug doxycycline hyclate in the form of lyophilisate to prepare solution for injections. During the development of the drug it was taken into account that aqueous doxycycline solution is pH dependent and tends to shift the solution pH during long-term storage. Therefore, excipients such as stabilizer and antioxidant providing buffering properties and stability of the solution were introduced into the composition. According to the research results an optimal composition of lyophilized powder was selected, the production technology with the stage of solution treatment with activated carbon was developed which allowed to obtain lyophilized powder with a well-formed porous mass without splits, cracks and fissures, resistant to shaking, and the prepared solution for parenteral administration is stable by the «Degree of coloration» quality indicator during accelerated storage regimen. It was found that doxycycline hyclate in the form of a lyophilisate shows a wide range of antibacterial activity. Comparative studies in vitro for two drugs, in the form of lyophilisate with doxycycline hyclate for injections and hard gelatin capsules with 100 mg of doxycycline hyclate, confirm equivalence of their bacteriostatic action against bacteria causing infectious diseases in humans.

Niosome encapsulated doxycycline-hyclate for potentiation of acne therapy: formulation and characterization

Acne is the pilosebaceous units' disorder. The most important cause of acne is the colonization of bacteria in the follicles. Among antibiotics, doxycycline-hyclate kills a wide range of bacteria. To prevent oral administration's side effects, overcome the barriers of conventional topical treatment, and improve the therapeutic effectiveness, doxycycline-hyclate was loaded into four niosomal formulations with different percentages of constituents (span 60 and cholesterol) prepared by the thin-film hydration method. Then, one of the four formulations with the most appropriate particle size of 362.88 ± 13.05 nm to target the follicles, percentage of drug entrapment efficiency of 56.3 ± 2.1%, in vitro drug release of 54.93 ± 1.99% after 32 hours, and the lowest permeation of the drug through the Wistar rat skin, was selected. Then, its toxicity on human dermal fibroblasts (HDF) by MTT method after 72 hours, its antibacterial activity against the main acne-causing bacteria via antibiogram test, and its effect on Wistar rat skin drug deposition were measured. Improved cell viability, increased antibacterial activity, and an approximately three-fold increase in drug deposition were the optimal niosomal formulation features relative to the free drug. Overall, this study demonstrated the ability of nano-niosomes containing doxycycline-hyclate to treat skin acne.