Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Shinde, Vikram R; Shelake, Makarand R.; Shetty, Sandeep S; Chavan-Patil, Amit B; Pore, Yogesh; Late, Sameer

doi:10.1211/jpp.60.9.0002

Cited by 52 publications

(28 citation statements)

References 45 publications

(30 reference statements)

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“…The possible mechanisms of increased dissolution rate of ETX sugar dispersions include reduction in drug particle size, carrier solubilization effect, absence of aggregation of drug crystallites, improved wettability and dispersibility of drug, dissolution of drug in hydrophilic carriers, conversion of drug to the amorphous state, or a combination of these methods (23)(24)(25). Because the dissolution enhancement of the quaternary maltose dispersion was less than that of ternary dispersions of the other two sugars, the maltose dispersions were not investigated any further.…”

Section: Results and Discussion In Vitro Dissolution Studiesmentioning

confidence: 99%

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Singh¹,

Chhabra²,

Pathak³

2011

Dissolution Technol.

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The current research was undertaken to develop and evaluate dissolution profiles of thermodynamically stabilized sugar dispersions of the poorly water-soluble, model drug etoricoxib (ETX). Fused-sugar dispersions were formulated using sorbitol, xylitol, and maltose separately, and the binary systems were stabilized by incorporation of the antiplasticizing agents poloxamer 407 and PVP K30 to obtain ternary and quaternary systems. The sugar dispersions (F1-F12) were subjected to in vitro dissolution studies, and based on model-independent dissolution parameters, ETX-sorbitol binary/ ternary/composite systems were selected for thermodynamic stability study. The aged ETX-sorbitol composite dispersion (SF8) displayed the highest percent dissolution efficiency (%DE 80min of 78.48), the minimum t 50% of 4.45 min, and the least tendency to recrystallize (D cryst of 0.68), confirming maximum amorphization and thermodynamic stability among all the composite dispersions. The SEM photomicrographs reveal complete miscibility of drug in the aged quaternary dispersion SF8, and its diffuse reflectance (DR) spectrum confirms the absence of any chemical change. Conclusively, sorbitol binary systems can be effectively stabilized by incorporation of PVP K30-poloxamer 407 and retain the dissolution characteristics of sugar dispersions upon aging.

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Section: Results and Discussion In Vitro Dissolution Studiesmentioning

confidence: 99%

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Singh¹,

Chhabra²,

Pathak³

2011

Dissolution Technol.

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“…Various formulation strategies were reported to improve its solubility and dissolution rate such as prodrug approach (5), nanosuspension (6), solid dispersion with polyethylene glycol and polyvinyl pyrollidone (7,8), complexation with cyclodextrins (8,9) and multicomponent molecular crystals such as solvates, salt, and cocrystals (10,11). Salts are usually formed between ionic drugs and the counter ions, and this approach has been used extensively to improve the solubility of BCS class II drugs.…”

Section: Introductionmentioning

confidence: 99%

Improvement of Physicochemical Properties of an Antiepileptic Drug by Salt Engineering

et al. 2012

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Abstract. The focus of the present investigation was to evaluate the feasibility of using cyclamic salt of lamotrigine in order to improve its solubility and intrinsic dissolution rate (IDR). The salt was prepared by solution crystallization method and characterized chemically by fourier transform infrared spectroscopy (FTIR), proton ( 1 H) and carbon ( 13 C) nuclear magnetic resonance (liquid and solid, NMR) spectroscopy, physically by powder X-ray diffraction (PXRD), thermally by differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), physicochemically for solubility, IDR, solution and solid-state stability, and polymorphism by solution recrystallization and slurry conversion studies. The FTIR, NMR, PXRD, DSC, and TGA spectra and thermograms indicated the salt formation. The salt formation increased lamotrigine solubility by 19-fold and IDR by 4.9-fold in water. The solution and solid-state stability were similar to parent molecule and were resistant to polymorphic transformation. In conclusion, cyclamic salt of lamotrigine provides another potential avenue for the pharmaceutical development of lamotrigine with improved physicochemical properties especially for pediatric population. It is also possible that appropriate dosage forms can be formulated with much lower drug amount and better safety profile than existing products.

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“…DSC thermogram of L-arginine indicated broad endothermic peaks at 49.36 °C, 99.97 °C and sharp endothermic peak at 222.64 °C due to dehydration of L-arginine and crystalline nature of it respectively [14,21]. In case of binary and ternary complexes, disappearance of bosentan monohydrate melting peaks were observed indicating the entrapment of bosentan monohydrate inside the β-cyclodextrin cavity confirming formation of inclusion complexes [25].…”

Section: Resultsmentioning

confidence: 89%

in silico and Physico-Chemical Assessment of Effectiveness of Hydroxy/Amino Acids as Auxiliary Substances to Improve the Complexation Efficiency of ββ ββ β-Cyclodextrin Towards Bosentan

Pore¹,

Jadhav²

2017

Asian J. Chem.

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The effectiveness of certain hydroxy and amino acids as an auxiliary substance to improve the complexation efficiency of β-cyclodextrin towards bosentan, a poorly soluble endothelin receptor antagonist, were assessed to enhance its physico-chemical performance. The phase solubility studies conducted in distilled water demonstrated a better choice of L-arginine as an auxiliary substance to improve complexation efficiency and association constant (Ks) of β-cyclodextrin. As a complementary evidence, in silico calculations were performed to foresee the stability, possible interactions and geometry of bosentan monohydrate inside β-cyclodextrin cavity, optimizing L-arginine again as an auxiliary substance. Subsequently, the solution state thermodynamic investigations revealed entropy driven complexation process. The lyophilized complexes were characterized by FTIR, DSC, XRPD and SEM. The performance of ternary complex was found to be appreciating in overall assessment, indicating better effectiveness of L-arginine as an auxiliary substance in improving complexation efficiency of β-cyclodextrin towards bosentan monohydrate.

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Enhanced solubility and dissolution rate of lamotrigine by inclusion complexation and solid dispersion technique

Cited by 52 publications

References 45 publications

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Dissolution Behavior and Thermodynamic Stability of Fused-Sugar Dispersions of a Poorly Water-Soluble Drug

Improvement of Physicochemical Properties of an Antiepileptic Drug by Salt Engineering

in silico and Physico-Chemical Assessment of Effectiveness of Hydroxy/Amino Acids as Auxiliary Substances to Improve the Complexation Efficiency of ββ ββ β-Cyclodextrin Towards Bosentan

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