Why is mannitol becoming more and more popular as a pharmaceutical excipient in solid dosage forms?

Abstract

Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient's body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.

A pragmatic approach for engineering porous mannitol and mechanistic evaluation of particle performance

“…Tablets made from mannitol fabricated at 110 -170°C showed significantly (ANOVA, p<0.001) higher porosity (0.30 ± 0.001 -0.53 ± 0.03) when compared to pure mannitol tablets (0.20 ± 0.002). This was consistent with the significantly lower (ANOVA, p<0.001) true density of spray dried mannitol (1.50 ± 0.003 -1.54 ± 0.004 g/cm 3 ) than pure mannitol (1.60 ± 0.002 g/cm 3 ). The powder made at 170°C showed significantly higher porosity (ANOVA/Tukey, p<0.05) than the rest of the powders which was attributed to particles elasticity and resistance to crushing (see discussion on elasticity measurements under physico-mechanical properties).…”

“…The last decade has seen the commercial introduction of a number of mannitol products with properties tailored to orally disintegrating dosage forms [2]. Popularity of mannitol was attributed to many factors including low hygroscopicity, inertness to APIs and development of robust tablets [3].…”

Application of general multilevel factorial design with formulation of fast disintegrating tablets containing croscaremellose sodium and Disintequick MCC-25

“…However, it could also be regarded as a sweetening agent. It has many physicochemical properties such as its sweet taste, cooling sensation that it leaves in the mouth, hygroscopicity and compactibility (Ohrem et al, 2014). It has also been shown that the use of mannitol in FDTs reduces disintegration time (Mizumoto et al, 2005;Chandraskhar et al, 2009).…”

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

“…Moreover, lactose is produced from bovine milk or with bovine-driven additives, thus it carries a potential risk of transmissible spongiform encephalopathy (EMA, 2002). Mannitol is valuable in the production of tablets due to its excellent mechanical compressing properties, physical and chemical stability (Ohrem et al, 2014). Toxicity studies indicated that mannitol did not cause any considerable adverse effects (Lawson, 2000).…”

“…Mannitol is an attractive pharmaceutical excipient that is becoming more and more popular in solid dosage forms (Ohrem et al, 2014). Mannitol shows the lowest hygroscopicity among the frequently used excipients as filler/binder and hence it can be utilized for moisturesensitive drugs.…”