Influence of mannitol concentration on the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol

Abstract

Mannitol is a pharmaceutical excipient that is receiving increased popularity in solid dosage forms. The aim of this study was to provide comparative evaluation on the effect of mannitol concentration on the physicochemical, mechanical, and pharmaceutical properties of lyophilised mannitol. The results showed that the physicochemical, mechanical and pharmaceutical properties of lyophilised mannitol powders are strong functions of mannitol concentration. By decreasing mannitol concentration, the true density, bulk density, cohesivity, flowability, netcharge-to-mass ratio, and relative degree of crystallinity of LM were decreased, whereas the breakability, size distribution, and size homogeneity of lyophilised mannitol particles were increased. The mechanical properties of lyophilised mannitol tablets improved with decreasing mannitol concentration. The use of lyophilised mannitol has profoundly improved the dissolution rate of indomethacin from tablets in comparison to commercial mannitol. This improvement exhibited an increasing trend with decreasing mannitol concentration. In conclusion, mannitols lyophilised from lower concentrations are more desirable in tableting than mannitols from higher concentrations due to their better mechanical and dissolution properties. Abbreviations∆H0, Endothermic enthalpy of CM melting; ∆Hs, Endothermic enthalpy of LM melting; ANOVA, One-way analysis of variance; API, Active pharmaceutical ingredient; c.opt, Optimal concentration; CI, Carr's index; CM, Commercial mannitol; Cman, Concentration of mannitol; d10%, particle size at 10% volume distribution; d50%, particle size at 50% volume distribution; d90%, particle size at 90% volume distribution; Db, Bulk density, DE, Dissolution efficiency; DSC, Differential scanning calorimeter; Dt, tap density; EB, Ease of breakage; Eq, Equation; FT-IR, Fourier transform infrared; GI, Gastro intestinal; HSD, Honestly Significant Difference; I, Relative intensity; Iamorphous, the input to the intensity from the amorphous region; Icrystalline, the input to the intensity from the crystalline region; LM, Lyophilised mannitol; MDR, Mean dissolution rate; MDT, Mean dissolution time; P, Statistical probability; PXRD, Powder X-ray diffraction; Q10min, The mean percentage of drug dissolved in the first 10 min; Q30min, The mean percentage of drug dissolved in the first 30 min; Q4min, The mean percentage of drug dissolved in the first 4 min; Q50min; The mean percentage of drug dissolved in the first 50 min; RDB, Relative degree of breakage;

Electrospinning scale-up and formulation development of PVA nanofibers aiming oral delivery of biopharmaceuticals

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Eplerenone nanocrystals engineered by controlled crystallization for enhanced oral bioavailability

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