QbD-based optimization of raloxifene-loaded cubosomal formulation for transdemal delivery: ex vivo permeability and in vivo pharmacokinetic studies.
Drug Deliv Transl Res
; 12(12): 2979-2992, 2022 12.
Article
in En
| MEDLINE
| ID: mdl-35462597
ABSTRACT
Raloxifene (RLX) is a drug that is commonly recommended to postmenopausal women at high risk of invasive breast cancer and to prevent osteoporosis. However, limited water solubility (0.000512 mg/ml) and low oral bioavailability (2%) of RLX limit its therapeutic utility. The objective of the present study was to develop an alternative transdermal delivery of RLX to improve its absorption, bypass first pass metabolism, and subsequently improve bioavailability. RLX-loaded cubosomes were prepared using the ethanol injection method followed by microfluidization technique and optimized using the QbD-based 23 factorial design. The average particle size, entrapment efficiency, and zeta potential of the optimized formulation were found to be 110.6 nm, 98.23%, and 26.2 mV, respectively. In vitro dissolution study indicated that the RLX-loaded cubosomes released 98.26% of the drug compared to pure RLX dispersion (58.6%). Histopathological examination revealed no sign of inflammation, indicating the safety of the developed formulation. Accelerated stability study as per ICH guidelines displayed no significant change in the formulation characteristics and drug-related performance of the developed formulation. Ex vivo permeability studies demonstrated a prolonged release from cubosomal formulation. In vivo pharmacokinetic studies revealed that the relative bioavailability of the optimized transdermal RLX-loaded cubosomes increased by 2.33-fold and 1.22-fold when compared with the oral RLX dispersion and transdermal RLX hydro-ethanolic solution respectively. IVIVC showed level C correlation with linear regression. Thus, the developed RLX-loaded cubosomes may have potential to overcome the problems associated with the existing marketed oral dosage forms of RLX.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Drug Carriers
/
Raloxifene Hydrochloride
Type of study:
Guideline
Limits:
Animals
/
Female
/
Humans
Language:
En
Journal:
Drug Deliv Transl Res
Year:
2022
Document type:
Article
Affiliation country:
India