Topical rapamycin formulations and their use in treating facial angiofibromas and other skin disorders
A local drug delivery technology for rapamycin, applied in skin diseases, antineoplastic drugs, aerosol delivery, etc., can solve the problems that the therapeutic effect cannot be ruled out and the results do not reach statistical significance
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Embodiment 1
[0102] Example 1: Pre-formulation
[0103] A modified isocratic method for the detection of rapamycin by high pressure liquid chromatography (HPLC) was used to efficiently detect a possible impurity / degradation product of rapamycin, rapamycin seco. HPLC analysis was performed on an Agilent 1200 instrument using a UV-Vis detector. The specifications of the two HPLC methods are as follows Table 1 shown. The first method, called RAP_1_LC.M, was linear in the range of 0.05 to 0.4 mg / ml with a correlation coefficient >0.999 and a relative standard deviation (RSD) percentage of less than 2% for replicate injections, making it adequate for pre-analysis. Preparation work. Figure 1A shown as HPLC chromatogram of a rapamycin standard eluting at or near the diluent front with possible impurity / degradation product rapamycin seco. In order to detect Seco rapamycin more accurately, a 10% to 55% acetonitrile gradient is used, and the gradient time is 2.5 to 15 minutes; the implement...
Embodiment 2
[0120] Example 2: Cream and Gel Excipient Formulations
[0121] A series of 1 cream and 2 gels was prepared. The gels of series 1 (gels 1A, 1B and 1C) used hydroxyethylcellulose (HEC) and the gels of series 2 (gels 2A, 2B and 2C) used carbomer 980 as the structure former. Cream series (cream A, cream B, cream C) use ceteareth-20 and cetostearyl alcohol, as follows table 5 in detail. Another major difference between the formulations tested was the solvent. Type "A" gels and creams use dimethylisosorbide (DMI), and type "B" gels and creams use diethylene glycol monoethyl ether ( or TC), "C" gels and creams use propylene glycol (PG).
[0122] Table 5: Cream and gel base excipients screened for structure forming ingredients
[0123]
[0124] *Cellulose hydroxyethyl ether 250HXX (Ashland)
[0125] **Polyoxyethylene 20 Stearyl Cetyl Ether
[0126] Each excipient base was formulated using one of three solvents identified in the pre-formulation work: "A" for 7.5% w / w D...
Embodiment 3
[0133] Example 3: Compounding and Stability Testing of Rapamycin
[0134] The compounding steps for a rapamycin formulation weighing 100-300 g are summarized below. During compounding, API dispersion uniformity is checked by microscopic examination of small samples. For API compounding, low shear mixing was performed using stainless steel propeller blades (1.5 inch diameter) and an IKA Eurostar 200 overhead mixer. High shear mixing was performed using a GLH homogenizer with a 10 mm stainless steel rotor-stator head.
[0135] Gel 1: Hydroxyethylcellulose (HEC) matrix
[0136] The hydroxyethylcellulose gel matrix should be obtained as follows: In the main container, add water (reserve 5% for rinsing), citrate (acid and salt), EDTA, glycerin (if used), poly Sorbitan Ester 80 and Benzyl Alcohol; mix on overhead mixer with propeller blades until homogeneous; add API; mix until solids are dispersed (10-20 min); start high shear mixing using 10mm rotor / stator homogenizer, cont...
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