Taste-masked and affordable donepezil hydrochloride orally disintegrating tablet as promising solution for non-compliance in Alzheimer's disease patients.
BACKGROUND
Manufacturing process and superdisintegrants used in orally disintegrating tablet (ODT) formulation are often time discussed. However, the effect of suitable filler for ODT formulation is not explored thoroughly.


OBJECTIVE
The aim of this study was to develop a novel taste masked and affordable donepezil hydrochloride ODT with fast disintegration time and stable to improve medication compliance of Alzheimer's disease patient.


METHODS
The ODT was manufactured using simple wet-granulation method. Crospovidone XL-10 was used as superdisintegrant and optimization was done by comparing the effect of three grades of lactose monohydrate compound as filler: Starlac®, Flowlac® and Tablettose®.


CONCLUSIONS
Formulations containing higher amount of colloidal silicon dioxide showed increase in hardness, weight, disintegration time and wetting time after stability study. Formulation E which containing 50% of Starlac® was found with shortest in vitro disintegration time (21.7 ± 1.67 s), in vivo disintegration time (24.0 ± 1.05 s) and in vitro disintegration time in artificial salvia (22.5 ± 1.67 s). Physical stability studies at 40 °C/75% RH for 6 months, Fourier transform infrared spectroscopy analysis and X-ray diffraction results showed that the formulation was stable. The drug-released profile showed that 80% of donepezil hydrochloride was released within 1 min. A single-dose, fasting, four-period, seven-treatment, double-blinded study involving 16 healthy human volunteers was performed to evaluate the palatability of ODT. Formulation VII containing 10 mg of ammonium glycyrrhizinate was able to mask the bitter taste of the drug.


CONCLUSIONS
The product has the potential to be commercialized and it might serve as solution for non-compliance among the Alzheimer's disease patients.
School of Pharmaceutical Sciences, Universiti Sains Malaysia , Minden, Penang , Malaysia.
Kai Bin
KB
Liew
Yvonne Tze Fung
YT
Tan
Kok Khiang
KK
Peh
D000328:Adult; D000544:Alzheimer Disease / Q000188:drug therapy / Q000191:economics; D000077265:Donepezil; D004311:Double-Blind Method; D004339:Drug Compounding; D016527:Drug Costs; D016503:Drug Delivery Systems / Q000009:adverse effects; D065546:Drug Liberation; D004355:Drug Stability; D004356:Drug Storage; D005079:Excipients / Q000008:administration & dosage* / Q000737:chemistry / Q000191:economics; D019695:Glycyrrhizic Acid / Q000008:administration & dosage* / Q000737:chemistry / Q000191:economics; D006244:Hardness; D006801:Humans; D007189:Indans / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000191:economics; D009061:Mouth Mucosa / Q000187:drug effects; D018697:Nootropic Agents / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000191:economics; D057240:Patient Preference; D010880:Piperidines / Q000008:administration & dosage* / Q000009:adverse effects / Q000032:analysis / Q000191:economics; D027544:Salvia / Q000737:chemistry; D013549:Sweetening Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000191:economics; D013607:Tablets; D013649:Taste; D055697:Taste Perception / Q000187:drug effects
D005079:Excipients; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D013549:Sweetening Agents; D013607:Tablets; D019695:Glycyrrhizic Acid; D000077265:Donepezil
Donepezil HCl; Flowlac; Starlac; Tablettose; non-compliance; orally disintegrating tablet