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

Abstract

The importance of mannitol has increased recently as an emerging diluent for orodispersible dosage forms. The study aims to prepare spray dried mannitol retaining high porosity and mechanical strength for the development of orally disintegrating tablets (ODTs).Aqueous feed of D-mannitol (10% w/v) comprising ammonium bicarbonate, NH 4 HCO 3 (5% w/v) as pore former was spray dried at inlet temperature of 110-170°C. Compacts were prepared at 20 kN and characterized for porosity, hardness and disintegration time. Particle morphology and drying mechanisms were studied using thermal (HSM, DSC and TGA) and polymorphic (XRD) methods.Tablet porosity increased from 0.20 ± 0.002 for pure mannitol to 0.53 ± 0.03 using fabricated porous mannitol. Disintegration time dropped by 50-77% from 135 ± 5.29 sec for pure mannitol to 75.33 ± 2.52 -31.67 ± 1.53 sec for mannitol 110 -170°C. Hardness increased by 150% at 110°C (258.67 ± 28.89 N) and 30% at 150°C (152.70 ± 10.58 N) compared to pure mannitol tablets (104.17 ± 1.70 N). Increasing inlet temperature resulted in reducing tablet hardness due to generation of 'micro-sponge'-like particles exhibiting significant elastic recovery. Impact of mannitol polymorphism on plasticity/elasticity cannot be ruled out as a mixture of α and β polymorphs formed upon spray drying.

Preparation of theophylline inhalable microcomposite particles by wet milling and spray drying: The influence of mannitol as a co-milling agent

“…As demonstrated by the energy vector diagram of mannitol ( Fig. 7d), intermolecular interaction forces extend parallel to the c crystallographic axis, clearly defining a slip direction along the (020) plane, in agreement with literature data (Al-Khattawi et al, 2015;Ho et al, 2012). Moreover it has been reported that mannitol crystals also fracture along the (011) plane (Ho et al 2012).…”

Combined control of morphology and polymorph in spray drying of mannitol for dry powder inhalation

“…6). Therefore, spray-dried mannitol was composed of a mixture of -mannitol and -mannitol, in agreement with previous findings [28,33]. Interestingly, variations in the concentration of NH 4 HCO 3 , as well as changes in the outlet temperature [28] and the concentration of the mannitol solution [33], leads to control of theand -mannitol ratio.…”

“…Therefore, spray-dried mannitol was composed of a mixture of -mannitol and -mannitol, in agreement with previous findings [28,33]. Interestingly, variations in the concentration of NH 4 HCO 3 , as well as changes in the outlet temperature [28] and the concentration of the mannitol solution [33], leads to control of theand -mannitol ratio. Moreover, the use of ethanol also favoured the formation of -mannitol, since an ethanol-water system has a higher drying rate compared to pure water under the same drying conditions [9,56].…”

“…NH 4 HCO 3 has been previously examined as an additive for spray drying [27], and was found to decompose into H 2 O , CO 2 , and NH 3 at temperatures above 50 , leaving no additive residue after spray drying. Further, NH 4 HCO 3 was seen to affect the morphology of drug particles during the spray-drying process [28].…”

Engineering Size and Structure of Particles in Novel Modified-Release Delivery Systems

“…On the other hand, the principle of templating could also be used to achieve the same purpose. For example, porous lactose particles were prepared by spray drying a solution containing lactose, whey protein isolate, and ethanol-soluble citric acid as a templating agent followed by the removal of citric acid by ethanol treatment (7). The achieved structure was a lactose network full of pores, which created a high specific surface area while preserving the strong structural stability of a highly crystalline powder.…”