Chloramphenicol palmitate suspensions

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.).

In a third precipitation method, the fact that most substances are more soluble at a high than at a low temperature is to made use of. A saturated solution is made at a high temperature after which it is cooled until supersamration is achieved. This last method is the least suitable because in practice it is often difficult to cool rapidly. The chloramphenicol palmitate suspension as described in Table 18.19 is an example of a suspension prepared by precipitation. Chloramphenicol palmitate precipitates when the solution in a hot mixture of polysorbate 80 and propylene glycol is mixed with the cold aqueous gel. By vigorous stirring during the final step, small particles are obtained. 

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).

Clements and Popli (1973) summarized transformation times during dissolution of pharmaceutical compounds from the literature. Theirstudy with meprobamate found that it took 168 h to convert to form I. Other than the example of chloramphenicol palmitate, this was much longer than most systems, which converted to the stable modiLcation in 300 s (theophylline) to 24 h (ampicillin). This is generally slow enough to allow therapeutic advantages to dosing the metastable solid orally, but too rapid to market suspensions of these forms with adequate physical stability. 

Synonyms. Chloramphenicol a-Palmitate Palmitylchloramphenicol. Proprietary Names. Chloromycetin Palmitate Suspension Globenicol. C27H42Cl2N206 = 561.5 CAS—530-43-8... 

Figure 1.13 Comparison of serum levels (pg cm obtained with suspensions of chloramphenicol palmitate after oral administration of a dose equivalent to 1.5 g of chloramphenicol.

Chloramphenicol has an extremely bitter taste. When this antibiotic is used orally, it should be formulated as a suspension, using the insoluble chloramphenicol palmitate. 

The surfactant in suspension formulations might minimize adhesional deposition by solubilization. Precipitation of chloramphenicol palmitate from solutions containing polysorbate 80 has been studied by Moes [50]. Low concentrations of the surfactant give coarse particles and large compact aggregates which on a macroscale have low sedimentation volumes. Systems with low concentrations of polysorbate 80 have higher apparent viscosities because of the aggregation of the particles. 

Chloramphenicol (Fig. 8.24) is an antibacterial agent that is used topically to treat infections of the eye and ear, but systemic treatment is reserved for treatment of life-threatening diseases such as those caused by Haemophilus influenzae and typhoid fever. Systemic administration through oral or parenteral delivery poses several problems chloramphenicol has a very bitter taste that cannot be masked effectively by conventional flavouring agents, which means there are therefore formulation problems that are needed to overcome poor patient acceptance. Additionally, poor water solubility makes formulation as an aqueous solution for parenteral administration difficult. Formation of the palmitate ester renders the compound virtually tasteless, and, whilst it remains relatively insoluble in water, it can be formulated as an oral suspension to enable good patient acceptance. Enzymatic... 

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