Studies On Isotretinoin Loaded Solid Lipid Nanaparticles Gel

Isotretinoin (IT) is a derivate of Vitamin A, which is the first generation tretinoin. IT is presumed to be the most effective drug for treatment of acne, especially for the severe acne. However, IT oral preparation on the market results serious side effect such as doing harm to mucous membrane, bone, nervous system and so on. And normal transdermal gel results severe skin irritation, which results from the degradation product when IT is exposure to light. It is necessary to introduce new pharmaceutics technique to ruduce side effect and increase therapeutic effect.In this paper, Isotretinoin loaded solid lipid nanoparticles (IT-SLN) with fine biocompatibility and its gel were prepared, and preparation and technological conditions of IT-SLN was studied and optimized; Also, method for in vitro drug release profile study and transdermal permeation study was established. The main results are as follows:(1)The excipients and formulation for IT-SLN was initial selected: ATO-5, soybean, and polysorbate 80. Film-sonication technique was introduced to prepare IT-SLN, and optimum condition for this technique was selected as follows: the rate of work was 600 W and work time was 15 min, respectively.(2)Further more, high-pressure micro fluidization technique was introduced to prepare IT-SLN. Optimum condition for this technique was selected as follows: speed and time for high speed stirring was 6000 r/min, 4 min, hot pre-emulsion passed through a high pressure micro fluidizer applying 2 cycles at 1200 bar. Zetasizer/Nano-ZS90 was selected to determine size/size distribution and zeta potential. Transmission electron microscope (TEM) studies showed that IT-SLN had a regular spherical or near spherical shape. IT-SLN was analyzed by DSC and XRD. Sephadex column was selected by determination of entrapment rate, HPLC was established by determination of entrapment rate and IT-SLN;Entrapment rate was selected as evaluation for L9(33)orthogonal to get optimization formulation for IT-SLN: the content for ATO-5, soybean, and polysorbate 80 was 3%, 3% and 3% respectively.(3)HPLC method was selected by determination of content determination of the IT-SLN gel. IT had a good linear relationship in the scope of 0.41 - 20.66μg/mL. It has high stability and good accuracy, the average coefficient of recovery was 100.6%. The prepared IT-SLN gel was uniformitily.(4)HPLC method was established to study in vitro drug release profile of IT-SLN, IT-SLN gel and IT gel. In vitro drug release profile showed that carbomer gel with menthol had more obvious permeation-enhancing effect than carbomer gel with azone. The higher viscosity of HPMC gel, the gel had smaller in vitro drug release and slow rate. The accumulate drug release of IT-SLN was a little more than IT-SLN HPC gel, while the accumulate drug release for IT-SLN HPC gel was much smaller than IT HPC gel. There was no much difference between this two kind viscosity of HPC gel for the accumulate drug release.(5)HPLC method was selected by measuring in vitro percutaneous permeability of IT-SLN, IT-SLN gel , IT-NLC, IT-NLC gel and IT HPC gel. The studies showed that: drug retention in mice skin of IT-SLN and IT-SLN Carbopol 940 gel was smaller than the other gel, while there was no obvious difference for drug retention in mice skin of IT-SLN HPC gel and IT HPC gel. More over, the drug retention in mice skin of IT-NLC and IT-NLC Carbopol 940 gel was lager than IT-NLC HPC gel and IT HPC gel. In vitro transdermal permeation profile for IT-SLN gel and IT-NLC gel needs further studied.