|
KMID : 1146920230530040517
|
|
Journal of Pharmaceutical Investigation
2023 Volume.53 No. 4 p.517 ~ p.526
|
|
|
Liquid-filled hard capsule formulation of choline alfoscerate: preparation and in vitro/in vivo evaluation
|
|
Woo Sang-Wook
Hwang Sung-Joo
Cho Cheong-Weon
|
|
|
Abstract
|
|
|
Purpose : The objective of this study was to develop a liquid-filled hard capsule (LFHC) formulation of choline alfoscerate (CA) by screening with empty capsules and excipients, and to assess its in vitro/in vivo activity by comparing with those of a commercially available soft gelatin capsule or tablet. CA is a common acetylcholine precursor in the brain, which has been used for the treatment of memory loss and cognitive malfunction. CA is highly hygroscopic, and deformation or leakage occurs when a commercial soft gelatin capsule or tablet is stored at high humidity.
Methods : LFHCs composed of hypromellose or gelatin were evaluated, and a compatibility study between excipients with a formulation including CA was conducted. CA and the selected excipient were encapsulated using a liquid-filling machine and sealed with a sealing machine. CA-loaded LFHCs were tested using an in vitro release study, stability test, and in vivo pharmacokinetic (PK) study with commercial soft gelatin capsules.
Results : CA was more stable in LFHCs with hypromellose capsules than LFHCs with gelatin capsules, and concentrated glycerin was a suitable excipient as a diluent in liquid formulation. The optimized formulation of LFHCs released CA (>?95%) within 30 min in distilled water. The stability of LFHCs with hypromellose capsules was also confirmed under long-term and accelerated conditions for 6 months. In harsh conditions, LFHCs with hypromellose capsules showed better physical stability than commercial soft gelatin capsules or tablets. In an in vivo PK study, the area under the plasma drug concentration?time curve (AUC0→t) of LFHCs with hypromellose capsules and soft gelatin capsules was 2.26?±?0.89 and 2.22?±?0.87 μg?h/mL, respectively; the maximum plasma concentration (Cmax) was 0.46?±?0.16 and 0.047?±?0.15 μg/mL, respectively; and the time to maximum peak concentration was 1.67 and 1.67 h, respectively. In addition, the calculated 90% confidence intervals of the geometric mean ratio of LFHCs to Gliatilin® for Cmax and AUC0→t were 0.978 (0.901, 1.063) and 1.053 (0.933, 1.190), respectively, and satisfied the bioequivalence acceptance criteria of 80.00?125.00%.
Conclusion : CA-loaded LFHCs with hypromellose capsules were more stable than other dosage forms, thereby making it an alternative formulation for the treatment of memory loss and cognitive malfunction.
|
|
|
KEYWORD
|
|
|
Choline alfoscerate, Liquid-filled hard capsules, Stability study, In vitro, In vivo study
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
|
|
|