β-galactosidase orodispersible dosage forms for the treatment of lactose intolerance

Abstract

Lactose intolerance is associated with the insurgence of mild to severe gastrointestinal symptoms. The administration of β-galactosidase (β-gal) tablets or capsules, which are unsuitable for the dysphagic population, is the main symptomatic treatment. This work aimed to demonstrate the feasibility of β-gal orodispersible films (ODF) prepared by solvent casting technique. Since the preparation involves thermal and mechanical stresses, which can compromise the enzyme stability, in vitro performances of ODF were compared to those of oral lyophilizates (OL).ODF were made of maltodextrin DE6, glycerol and Capryol®90. OL made of different grades of maltodextrins, and sorbitol or trehalose were prepared in aluminium blisters. ODF and OL were assayed for disintegration time and β-gal activity. The hydrolysis rate of lactose was determined using: a) a placebo capsule (500 mg lactose) disintegrated in a glass of water; b) 150 mL milk in biorelevant media. ODF (6 cm2) and OL (made of maltodextrin DE19 and trehalose). ODF and OL loaded with about 4000 UI of β-gal were stable over 3 months of storage at 25 °C/60% RH. Both of them allowed the hydrolysis of lactose in water within 15 min. The complex composition of milk affected the hydrolysis rate (K) of lactose: the reaction was faster in fasted-state media (K ≈ −0.07 min−1) than in those simulating the fed state of subjects with physiologically appreciable residual gastric fluid in the stomach (grade 1 antrum: 20 mL, K ≈ −0.005 min−1; grade 2 antrum: 180 mL, K ≈ −0.01 min−1). No significant differences were noticed between ODF and OL. Overall, ODF can be proposed to hydrolyse lactose contained in immediate release dosage forms, improving the patient's adherence to therapy. Moreover, the dependence of the lactose degradation kinetic not only on the fed or fasted conditions, but also on the antrum phenotype may allow the development of ODF in a more patient-centric perspective.