Lidocaine free base

Lidocaine free base at 10% w/v is formulated into a pump spray for use in dentistry and obstetrics. 

For other drugs that have tertiary, secondary, and primary nitrogens, the pKa values of the individual compounds are important in predicting retention when varying the pH of the mobile phase [320]. For example, the retention of phenylpropanolamine with a pKa of 9.0 rapidly decreases as it becomes the free base at a pH greater than 8. For lidocaine with a pKa of 7.9, the formation of its free base and decrease of retention occur at a pH greater than 7. In compounds such as benzocaine, which has a pKa at 2.8, little or no change occurs with pH variation in the mobile phase [3]. 

Lidocaine is a local anaesthetic which is available as a free base and hydrochloride salt. Lidocaine base is known to form eutectic mixture with prilocaine base and this eutectic mixture forms a dispersed phase of EMLA emulsion cream. Shukla et al. reported that with the help of microemulsification, the drug loading can be increased from 5% (present in EMLA cream) to 20% which may result in quick action by virtue of higher concentration gradient across the skin [49]. 

A choice of salts can also expand the formulation options for a material. The antimalarial agent a-(2-piperidyl)-3,6-bis(trifluoromethyl)-9-phenanthrene-methanol hydrochloride (Fig. 9) exhibited poor solubility, was delivered as an oral formulation, and required a single dosing of 750 mg (13). Seven salts and the free base were evaluated. The lactate salt was found to be 200 times as soluble as the hydrochloride salt (Table 3). This enhanced solubility would make it possible to reduce the oral dose to achieve the same therapeutic response as well as develop a parenteral formulation for the treatment of malaria. However, the case of lidocaine hydrochloride (Fig. 14) demonstrates that a compound limited to parenteral and topical formulations can be expanded to oral administration by changing to a salt form with acceptable physical properties (16). The hydrochloride salt was hygroscopic, difficult to prepare, and hard to handle. Six salts were evaluated for salt formation, solubility, and hygroscopicity. Other salts, such as phosphate, exhibited properties acceptable for dry pharmaceutical dosage forms. 

Isolation of 25 involves filtering the reaction mixture to remove the diethylammonium hydrochloride, followed by extraction of the basic 25 into aqueous hydrochloride. All nonbasic contaminants, such as unchanged 37, remain in the toluene solution. Lidocaine is liberated from its hydrochloride acid salt with aqueous base and then extracted into diethyl ether. After removal of the diethyl ether, the lidocaine is isolated as a low-melting solid or oil, depending upon its purity. In order to facilitate purification of lidocaine in this procedure, it is converted into its solid bisulfate salt 42 by reaction with sulfuric acid (Eq. 21.24). Many drugs that contain a basic site, like lidocaine, are sold in the form of their hydrochloride or sulfate salts because these salts are typically more stable and more soluble in water than the free base. 

Creams typically contain lidocaine and prilocaine free bases both at 2.5% w/w. Prilocaine does not affect the CNS as much as lidocaine but it does have toxicity problems of its own (see below). 

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