2,3-dihydroxypropyl octanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Clarithromycin was obtained as the free base from Wockhardt (Delhi, India). Vitamin E Succinate (VESA) was obtained from Eastman (Freeport Tenn.). Capmul® MCM was obtained from Abitec (Janesville Wis.); Poloxamer® 407 (Pluronic® F-127) from BASF (Parsippany N.J.); PEG-400 from Spectrum Chemicals (Gardenia Calif.), and d-δ-tocopherol from Sigma Chemicals (St Louis MO). An oil phase consisting of d-δ-tocopherol and Capmul MCM was prepared using 2 parts of δ-tocopherol. Surfactant and clarithromycin were then added as shown in the table below. Dry ethanol was used to dissolve the components at 70° C. and the ethanol was then removed under vacuum. A clear amber oil resulted, but upon cooling, oblong, “casket-lid” crystals of clarithromycin were observed. A tocol-soluble ion pair of this compound was then produced by addition of a stoichiometric equivalent of Vitamin E succinate (VESA) as the free acid. On re-dissolution in ethanol and cooling no crystals formed. The clarithromycin was now sufficiently soluble in the tocopherol oil to allow subsequent preparation of the emulsion. The oil was then re-heated to 45° C. and degassed immediately prior to emulsification as described below. was prepared to dissolve the components at 70° C. the ethanol was then removed under vacuum A clear amber oil resulted upon cooling

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Clarithromycin was obtained as the free base from Wockhardt (Delhi, India). Vitamin E Succinate (VESA) was obtained from Eastman (Freeport Tenn.). Capmul® MCM was obtained from Abitec (Janesville Wis.); Poloxamer® 407 (Pluronic® F-127) from BASF (Parsippany N.J.); PEG-400 from Spectrum Chemicals (Gardenia Calif.), and d-δ-tocopherol from Sigma Chemicals (St Louis MO). An oil phase consisting of d-δ-tocopherol and Capmul MCM was prepared using 2 parts of δ-tocopherol. Surfactant and clarithromycin were then added as shown in the table below. Dry ethanol was used to dissolve the components at 70° C. and the ethanol was then removed under vacuum. A clear amber oil resulted, but upon cooling, oblong, “casket-lid” crystals of clarithromycin were observed. A tocol-soluble ion pair of this compound was then produced by addition of a stoichiometric equivalent of Vitamin E succinate (VESA) as the free acid. On re-dissolution in ethanol and cooling no crystals formed. The clarithromycin was now sufficiently soluble in the tocopherol oil to allow subsequent preparation of the emulsion. The oil was then re-heated to 45° C. and degassed immediately prior to emulsification as described below. was prepared to dissolve the components at 70° C. the ethanol was then removed under vacuum A clear amber oil resulted upon cooling

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Octanoyl-rac-glycerol (10.00 g, 45.81 mmol) and DMAP were placed in a flame-dried round bottom flask, followed by triethylamine (13.0 ml, 93.27 mmol) and CH2Cl2 (200 ml). When the solid dissolved, trityl chloride (14.07 g, 50.47 mmol) was added and the mixture was stirred at room temperature for two days. The mixture was poured into ice water and the two phases were separated. The organic layer was washed three times with 1 N HCL and twice with water, dried over MgSO4, and evaporated. The product was purified by chromatography in two batches, (150 g silica gel each with hexanes:ethyl acetate (8:1) solvent) to yield compound 43, 1-octanoyl-3-O-trityl-rac-glycerol (9.96 g, 47% yield). When the solid dissolved the two phases were separated The organic layer was washed three times with 1 N HCL twice with water, dried over MgSO4 evaporated The product was purified by chromatography in two batches

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Clarithromycin was obtained as the free base from Wockhardt (Delhi, India). Vitamin E Succinate (VESA) was obtained from Eastman (Freeport Tenn.). Capmul® MCM was obtained from Abitec (Janesville Wis.); Poloxamer® 407 (Pluronic® F-127) from BASF (Parsippany N.J.); PEG-400 from Spectrum Chemicals (Gardenia Calif.), and d-δ-tocopherol from Sigma Chemicals (St Louis MO). An oil phase consisting of d-δ-tocopherol and Capmul MCM was prepared using 2 parts of δ-tocopherol. Surfactant and clarithromycin were then added as shown in the table below. Dry ethanol was used to dissolve the components at 70° C. and the ethanol was then removed under vacuum. A clear amber oil resulted, but upon cooling, oblong, “casket-lid” crystals of clarithromycin were observed. A tocol-soluble ion pair of this compound was then produced by addition of a stoichiometric equivalent of Vitamin E succinate (VESA) as the free acid. On re-dissolution in ethanol and cooling no crystals formed. The clarithromycin was now sufficiently soluble in the tocopherol oil to allow subsequent preparation of the emulsion. The oil was then re-heated to 45° C. and degassed immediately prior to emulsification as described below. was prepared to dissolve the components at 70° C. the ethanol was then removed under vacuum A clear amber oil resulted upon cooling