title: Quality by design coupled with near infrared in formulation of transdermal glimepiride liposomal films.
abstract: This study is aimed at developing glimepiride (GMD) liposomal films using quality by design (QbD) and process analytical technology (PAT) principles. Risk analysis and Plackett-Burman design were utilized to evaluate formulation variables in two paths. Internal path included liposomal parameters (phosphatidylserine, cholesterol and drug concentrations, and pH of hydration medium). External path constituted films parameters, namely, polymer, plasticizer, and permeation enhancer percentages. As a PAT tool, near infrared (NIR)-based chemometric analysis was used in quantifying GMD contents. Liposomal formulations showed maximum GMD entrapment capacity of 41.9% with vesicular size of 0.51 μm at phospholipid to cholesterol to drug weight ratio of 2:1:0.8. Its transdermal films showed elongation ratio of 75%, folding endurance of 700-fold, 16.6% and 26.8% drug release after 1 and 12 h, respectively. Moreover, 3D response spaces for GMD entrapment and release characteristics were established. Regarding NIR analysis, partial-least-square regression model was accurate in quantifying drug content as indicated by the low root-mean-squared error of calibrations and prediction of 0.031 and 0.032, and bias values of 0.0015 and 0.0021, respectively. In conclusion, this study highlights the level of understanding that can be accomplished through a well-designed research based on QbD and PAT paradigms.
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors: Osama Abdelhakim Aly
authors: OAA
authors: Ahmed
authors: Polymer Research Laboratory, Department of Chemistry, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Mallesh
authors: M
authors: Kurakula
authors: Department of Clinical Biochemistry, Faculty of Medicine, King Abdulaziz University, Jeddah, Saudi Arabia.
authors: Zainy Mohamed
authors: ZM
authors: Banjar
authors: Department of Pharmaceutics and Pharmaceutical Technology, Faculty of Pharmacy, Al-Azhar University, Cairo, Egypt.
authors: Mohsen Ibrahim
authors: MI
authors: Afouna
authors: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: aszidan@kau.edu.sa.
authors: Ahmed Samir
authors: AS
authors: Zidan
mesh_terms: D000279:Administration, Cutaneous; D002784:Cholesterol / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D008081:Liposomes / Q000737:chemistry*; D010718:Phosphatidylserines / Q000737:chemistry; D012867:Skin / Q000378:metabolism; D013055:Spectrophotometry, Infrared; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D057968:Transdermal Patch
chemical_list: D007004:Hypoglycemic Agents; D008081:Liposomes; D010718:Phosphatidylserines; D013453:Sulfonylurea Compounds; C057619:glimepiride; D002784:Cholesterol
keywords: Formulation; Infrared spectroscopy; NIR; Percutaneous; Placket-Burmann design; Transdermal drug delivery; glimepiride; liposomes; transdermal film