Chloramphenicol-3-palmitate

Detreomine - Chloromphenicoi Detreopal - Chloramphenicol palmitate Dettol - 4-Chloro-3,5 Xyleno ... 

Fig. 21 Comparison of mean blood serum levels obtained with chloramphenicol palmitate suspensions containing varying ratios of A and B polymorphs, following a single oral dose equivalent to 1.5 g of chloramphenicol. Percentage of polymorph B in the suspension M, 0% N, 25% O, 50% P, 75% L, 100%. (From Ref. 37.).

Tables 3 and 4 list thermodynamic values calculated for polymorphs of chloramphenicol palmitate and mefenamic acid, respectively. Absorption studies of chloramphenicol palmitate in humans show that suspensions containing polymorph B of chloramphenicol palmitate gave blood levels approximately 10 times higher than those produced by suspensions of polymorph A [49], This may be due to the significant (-774 cal/mol) free energy difference between the polymorphs resulting in a substantial difference in their solubility and dissolution behavior. This theory is supported by the almost identical blood levels due to polymorphs I and n of mefenamic acid, which have a small free energy difference (-231 cal/mol) and similar solubility and dissolution behavior (Table 4).

As in the case of chloramphenicol palmitate, it may be desirable to have the more soluble (less stable) polymorph of a drug. One method, based on thermo-... 

Figure 14 Dissolution curves for polymorphs A and B of chloramphenicol palmitate in 35% terf-butanol and water at 30°C and 38°C. (O) Polymorph A at 30° (A) polymorph B at 30° ( ) polymorph A at 38° ( ) polymorph B at 38°C. (Reprinted with permission from Ref. 48.)...

Table 3 Thermodynamic Values for Polymorphs of Chloramphenicol Palmitate... 

MM deVilliers, JG Van der Watt, AP l.otter. Interconversion of the polymorphic forms of chloramphenicol palmitate (CaP) as a function of environmental temperature. Drug Dev Ind Pharm 17(10) 1295—1303, 1991. 

AJ Aguiar, J Krc, AW Kinkel, JC Samyn. Effect of polymorphism on the absorption of chloramphenicol from chloramphenicol palmitate. J Pharm Sci 56 847, 1967. 

When drug polymorphs cannot interconvert as a result of being suspended in aqueous solution, a different bioavailability of the two forms usually results [126], For instance, the peak concentration of chloramphenicol in blood serum was found to be roughly proportional to the percentage of the B-polymorph of chloramphenicol palmitate present in a matrix of the A-polymorph [133]. The same concept has been found to apply to hydrate species, where the higher solubility and dissolution rate of the anhydrous phase relative to the trihydrate phase resulted in measurably higher blood levels when using the anhydrate as... 

Examples Infrared spectroscopy is employed to compare samples of chloramphenicol palmitate (biologically active form) recovered from chloramphenicol palmitate mixture vis-a-vis an artificially prepared mixture of authentic sample consisting 10 per cent of the inactive polymorph . 

R. Chenevert, R. Pouliot, P. Bureau, Enantioselective Hydrolysis of -Chloramphenicol Palmitate by Hydrolases , Bioorg. Med. Chem. Lett. 1994, 4, 2941-2944. 

Absorption - Chloramphenicol base is absorbed rapidly from the intestinal tract and is 75% to 90% bioavailable. The inactive prodrug, chloramphenicol palmitate, is rapidly hydrolyzed to active chloramphenicol base. Bioavailability is approximately 80% for the palmitate ester. The bioavailability of the IV... 

The usual dosage of chloramphenicol is 50-100 mg/kg/d. After oral administration, crystalline chloramphenicol is rapidly and completely absorbed. A 1-g oral dose produces blood levels between 10 and 15 mcg/mL. Chloramphenicol palmitate is a prodrug that is hydrolyzed in the intestine to yield free chloramphenicol. The parenteral formulation is a prodrug, chloramphenicol succinate, which hydrolyzes to yield free chloramphenicol, giving blood levels somewhat lower than those achieved with orally administered drug. Chloramphenicol is widely distributed to virtually all tissues and body fluids, including the central nervous system and cerebrospinal fluid, such that the concentration of chloramphenicol in brain tissue may be equal to that in serum. The drug penetrates cell membranes readily. 

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