Chloramphenicol solubilization

There are a large number of publications and papers in which the increase in absolute solubility of active substances by povidone has been tested and described. However, if the selection is restricted to the low-molecular types, this number becomes significantly smaller (Table 93). Naturally, a solubilization effect can also be expected of povidone K 12 and povidone K17, even if such an effect is reported in the literature only for the medium-molecular povidone (see Table 97), though the amounts of active substance complexed may differ according to the molecular weight of povidone (see Table 92). However, the influence of the molecular weight depends very much on the active substance with trimethoprim and chloramphenicol it is very large, while with phenobarbital it is small. 

The solubilization of active substances, such as chloramphenicol, in eye drops is described in Section 2.4.5.5, Table 99. 

Surfactants The use of surfactants is greatly restricted in formulating ophthalmic solutions. The order of surfactant toxicity is anionic > cationic nonionic. Several nonionic surfactants are used in relatively low concentrations to aid in dispersing steroids in suspensions and to achieve or to improve solution clarity. Those principally used are the sorbitan ether esters of oleic acid (polysorbate or Tween 20 and 80), polymers of oxyethylated octyl phenol (tyloxapol), and polyoxyl 40 stearate. The lowest concentration possible is used to perform the desired function. Their effect on preservative efficacy and possible binding by macromolecules as well as effect on ocular irritation must be taken into account. The use of surfactants as cosolvents for an ophthalmic solution of chloramphenicol has been described (347). This composition includes polyoxyl 40 stearate and polyethylene glycol to solubilize 0.5% chloramphenicol. These surfactants-cosolvents provide a clear... 

Carboxylic half-esters (e.g. hemisuccinates) of phenols are easily hydrolyzed in aqueous solution and are therefore not recommended for the solubilization of phenolic compounds. Even hemisuccinates of alcohols suffer somewhat from stability problems and must be supplied as lyophi-lized (freeze-dried) powders for reconstitution in water and used within 48 h (see, for example, the monographies chloramphenicol sodium succinate or hydrocortisone sodium succinate in The Handbook on Injectable Drugs,see also Anderson et... 

FIGURE 39.6 Solubilization of chloramphenicol by surfactants. Squares, cetrimide black circles, sodium laurylsulfate empty circles, polysorbate 80 triangles, PEG 40 monostearate. 

TABLE 39.6 Parameters of the Solubilization of Chloramphenicol by Surfactants. Solubilization of chloramphenicol by surfactants... 

The solubilization of chloramphenicol with one member each of four classes of surfactants is shown in Figure 39.6 while Table 39.6 gives the key parameters of the surfactants. 

The solubilization of chloramphenicol with one member each of four classes of surfactants is shown in Fig. 37.7, while Table 37.5 gives the respective parameters. The typically linear relationship in micellar solubilization is obvious in the graph Fig. 37.7. In Table 37.5, the respective data reflecting the solubilization power of the surfactants are presented. 

Chloramphenicol, soluble 1 in 400 of water at 20° C and 1 in 7 of propylene glycol, has been solubilized in Tween solutions [92,93]. In spite of its superior solubility in propylene glycol, this compound cannot be used as a solvent for chloramphenicol in eye-drops or nasal preparations since it causes a marked burning sensation. Simple aqueous solutions of chloramphenicol lose about half their antibiotic activity by hydrolysis on storage for 290 days at 20 to 22° C [94]. 

Chloramphenicol 1 %, polysorbate 80 6 %, in water for injection has been suggested as an ophthalmic solution [95]. Other formulae have been given and some of these are collected in Table 6.10. A solution of the antibiotic has been prepared in 50% iV,iV-dimethylacetamide as an intravenous injection. N,N-dimethylacetamide is a hydrotropic substance, a group of compounds whose actions are discussed in Section 6.7. Different crystal forms of chloramphenicol palmitate are soluble to differing extents in solutions of polysorbate 60. A detailed study of the solubilization of chloramphenicol in cetomacrogol solutions has been reported by Rogers [98] Regdon-Kiss and Kedvessy [99] have studied the... 

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. 

Uses Solvent, solubilizer for phamtaceulicals chem. reaction medium reaction solvent in many syntheses ind. vitamin E precursor solubilizer for topicals for applic. to human or animal hair, skin bioavailability enhancer for topicals skin penetration enhancer extraction solvent bioadhesive spray bandages Features Nonaq. increases water sol. of chloramphenicol, procaine, other therapeutic compds. increases sol n. stability of drugs in aq. sol n. 

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