The Application of Modified Flow-Through Cell Apparatus for the Assessment of Chlorhexidine Dihydrochloride Release from Lozenges Containing Sorbitol

Abstract

Abstract. The objective of this work was to apply a new apparatus for the assay of the drug release from lozenge tablet with a potential use in the treatment of oral candidosis and another conditions connected to microbial etiopathology in the oral cavity or as an antiplaque factor. Also, an approach to comparison of the applied method with the classical paddle apparatus method was performed. Tablets containing chlorhexidine dihydrochloride were formulated with granulated sorbitol of different grades (diameter of 110, 180, 480, and 650 μm, respectively), lactose, and magnesium stearate as excipients. Tablets were obtained through direct compression, and uniformity of weight, friability, breaking strength, disintegration, and release rate were evaluated. The disintegration times ranged between 10 and 21 min. In the next stage of the study, the release of chlorhexidine from lozenges prepared with granulated sorbitol grade 110 μm and different amounts of lactose and magnesium stearate was assessed. Two stages were observed during the release of chlorhexidine dihydrochloride from the lozenges, assayed by the classical paddle apparatus method II USP. In the first stage, release rates were between 2.6×10 −2 and 4.7×10, in the second stage between 1.7×10 −3 and 7.7×10. In the case of the in-house method, the release was near to first-order kinetics through the entire release experiment, with rate constants between 3.6×10 −2 and 6.6×10 −2 min −1 . The sorbitol granulate of granules with diameter 110 μm was found to be most suitable for the lozenges with chlorhexidine dihydrochloride and lactose. The in-house release method, proposed in this work, seems to be more realistic for the preliminary assessment of predicted drug concentrations in the oral cavity after the intake of a lozenge.

Applications of various forms of chlorhexidine in dentistry – a review

“…The crucial parameter in the formulation of a tablet with chlorhexidine would be the concentration of the drug in the oral cavity during the application of the lozenge. In the case of antimicrobial substances, like chlorhexidine salts, the prolonged presence of the active substance in the minimal inhibition concentration (MIC) or the minimal bactericidal concentration (MBC) is of great importance [32]. Chlorhexidine lozenges have a role in plaque control also.…”

Biopharmaceutic IVIVE—Mechanistic Modeling of Single- and Two-Phase In Vitro Experiments to Obtain Drug-Specific Parameters for Incorporation Into PBPK Models

“…8,9 A number of techniques have been employed to achieve sink or near sink conditions viz. (1) increasing the dissolution media volume (typically up to 900-1000 mL in USP I and II apparatus), (2) addition of solubility enhancers such as surfactants, 10 (3) continuous media change flow through cell (USP IV) apparatus, [11][12][13] (4) integrating sink dialysis bag, or (5) use of an additional (organic) phase into which drug can partition. [14][15][16][17][18] The 2-phase in vitro system contains an aqueous medium within which the drug product undergoes dissolution and an additional (immiscible) organic layer to simulate an absorptive sink.…”

“…As these same mathematical models have integrated within main PBPK simulator, these parameters estimated against the in vitro system can be used for in vivo extrapolation. 12 To assess the performance of biopharmaceutical IVIV_E and provide a proof of concept, we recently presented a stepwise in vitro data modeling approach using weakly basic drugs such as ketoconazole 20 and posaconazole, 21 known to precipitate in vivo and its impact of in vivo predictions from a PBPK model.…”