Precipitation-lyophilization-homogenization (PLH) for preparation of clarithromycin nanocrystals: influencing factors on physicochemical properties and stability.
Nanocrystals is one of effective technologies used to improve solubility and dissolution behavior of poorly soluble drugs. Clarithromycin is classified in BCS class II having low bioavailability due to very low dissolution behavior. The main purpose of this study was to investigate an efficiency of clarithromycin nanocrystals preparation by precipitation-lyophilization-homogenization (PLH) combination method in comparison with high pressure homogenization (HPH) method. The factors influencing particle size reduction and physical stability were assessed. The results showed that the PLH technique provided an effective and rapid reduction of particle size of nanocrystals to 460 ± 10 nm with homogeneity size distribution after only the fifth cycle of homogenization, whereas the same size was attained after 30 cycles by the HPH method. The smallest nanocrystals were achieved by using the combination of poloxamer 407 (2%, w/v) and SLS (0.1%, w/v) as stabilizers. This combination could prevent the particle aggregation over 3-month storage at 4 °C. The results from SEM showed that the clarithromycin nanocrystals were in cubic-shaped similar to its initial particle morphology. The DSC thermogram and X-ray diffraction pattern of nanocrystals were not different from the original drug except for intensity of peaks which indicated the presenting of nanocrystals in the crystalline state and/or partial amorphous form. In addition, the dissolution of the clarithromycin nanocrystals was dramatically increased as compared to the coarse clarithromycin.
Excellent Center of Innovative Drug Delivery and Nanomedicine, Faculty of Pharmacy, Mahidol University, Rajathevee, Bangkok 10400, Thailand; Department of Pharmacy, Faculty of Pharmacy, Mahidol University, Rajathevee, Bangkok 10400, Thailand.
Boontida
B
Morakul
Jiraphong
J
Suksiriworapong
Jiraporn
J
Leanpolchareanchai
Varaporn Buraphacheep
VB
Junyaprasert
D011232:Chemical Precipitation; D017291:Clarithromycin / Q000737:chemistry*; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005612:Freeze Drying; D053758:Nanoparticles / Q000737:chemistry*; D020442:Poloxamer / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry
D005079:Excipients; D013501:Surface-Active Agents; D020442:Poloxamer; D017291:Clarithromycin
Clarithromycin; HPH; High pressure homogenization; Nanocrystals; PLH; Poorly soluble drug; Precipitation-lyophilization-homogenization; high pressure homogenization; precipitation-lyophilization-homogenization