Surfactant‐facilitated crystallization of dihydrate carbamazepine during dissolution of anhydrous polymorph

Abstract

The influence of two structurally different anionic surfactants on the anhydrous-to-dihydrate transformation of carbamazepine (CBZ) was investigated. The surfactants studied were sodium lauryl sulfate (SLS), a surfactant commonly used in compendial dissolution methods, and sodium taurocholate (STC), an important surfactant in the solubilization and absorption of drugs and lipids in the gastrointestinal tract. Results show that both surfactants promoted the crystallization of CBZ dihydrate [CBZ(D)] during dissolution of the anhydrous monoclinic polymorph [CBZ(A)]). Examination of crystal surfaces showed that SLS facilitated the surface-mediated nucleation of CBZ(D) on CBZ(A) crystals at surfactant concentrations below the critical micelle concentration (cmc). Solubilization of a dye and related color changes provided visual evidence for adsorbed SLS assemblies on CBZ(A) crystal faces below the cmc. Above the cmc, both surfactants promoted the transformation by increasing the bulk nucleation of CBZ(D). STC changed the crystal morphology of CBZ(D) from acicular to prismatic, depending on STC concentration. Such morphology changes originate from interactions between STC and molecular structures of CBZ(D) crystal faces that interfere with the formation of a hydrogen-bonded chain of water molecules and carboxamide dimers.

Mathematical Models to Explore Potential Effects of Supersaturation and Precipitation on Oral Bioavailability of Poorly Soluble Drugs

“…The in vitro peak drug concentration and peak duration produced by supersaturating dosage forms are highly dependent on the drug, drug form, formulation components, and solution composition (5,(28)(29)(30)(31)(32)(33)38,39,(48)(49)(50). To bracket a range of bioavailability that could be reasonably expected from supersaturating dosage forms, two alternative assumptions were used: either (a) the duration of the peak drug concentration in vivo corresponds to the in vitro data or b) the drug concentration in vivo reaches the peak concentration observed during in vitro dissolution.…”

“…Important factors to consider when performing dissolution experiments are temperature, hydrodynamics, and medium selection (28)(29)(30)(31)(32)(33). For example, the addition of bile salts and/or phospholipids has been shown to alter drug precipitation kinetics (33) by effecting the nucleation and/or crystal growth rate (28,51).…”

“…Here, we seek to capture the main features of each curve with a minimum number of parameters, allowing rapid characterization. Of course, the use of biological relevant medium and volumes will provide better input (28)(29)(30)(31)(32)(33). To be sure, there is some loss in accuracy when a minimum number of parameters are used to characterize a wide variety of peak shapes.…”

Art of Synthesis of Desired Polymorphs: A Review

“…In recent years, several new techniques have been developed for nucleation. Additionally, some recent developments in crystallization techniques also contribute towards this goal [8][9][10][11][12]. Different techniques for the generation of polymorphs are presented here.…”

Solution-Mediated Phase Transformation of Haloperidol Mesylate in the Presence of Sodium Lauryl Sulfate

“…Solution-mediated phase conversion of more soluble forms to lower solubility forms during dissolution is hypothesized to occur in three steps: (1) dissolution to create a supersaturated solution, (2) nucleation of less soluble phase, and (3) growth of that phase (5). The occlusion of the more soluble form often occurs by the growth of the less soluble phase on the dissolving surface, greatly reducing the enhanced dissolution rate one hoped to gain by forming a more soluble solid (6)(7)(8).…”