title: QbD-Enabled Development of Novel Stimuli-Responsive Gastroretentive Systems of Acyclovir for Improved Patient Compliance and Biopharmaceutical Performance.
abstract: The current studies entail systematic quality by design (QbD)-based development of stimuli-responsive gastroretentive drug delivery systems (GRDDS) of acyclovir using polysaccharide blends for attaining controlled drug release profile and improved patient compliance. The patient-centric quality target product profile was defined and critical quality attributes (CQAs) earmarked. Risk assessment studies, carried out through Ishikawa fish bone diagram and failure mode, effect, and criticality analysis, helped in identifying the plausible risks or failure modes affecting the quality attributes of the drug product. A face-centered cubic design was employed for systematic development and optimization of the concentration of sodium alginate (X 1) and gellan (X 2) as the critical material attributes (CMAs) in the stimuli-responsive formulations, which were evaluated for CQAs viz. viscosity, gel strength, onset of floatation, and drug release characteristics. Mathematical modeling was carried out for generation of design space, and optimum formulation was embarked upon, exhibiting formulation characteristics marked by excellent floatation and bioadhesion characteristics along with promising drug release control up to 24 h. Drug-excipient compatibility studies through FTIR and DSC revealed absence of any interaction(s) among the formulation excipients. In vivo pharmacokinetic studies in Wistar rats corroborated extension in the drug absorption profile from the optimized stimuli-responsive GR formulations vis-à-vis the marketed suspension (ZOVIRAX®). Establishment of in vitro/in vivo correlation (IVIVC) revealed a high degree of correlation between the in vitro and in vivo data. In a nutshell, the present investigations report the successful development of stimuli-responsive GRDDS of acyclovir, which can be applicable as a platform approach for other drugs too.
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014. bsbhoop@yahoo.com.|UGC-Centre of Excellence in Applications of Nanomaterials, Nanoparticles & Nanocomposites Biomedical Sciences, Panjab University, Chandigarh, India, 160 014. bsbhoop@yahoo.com.
authors.forename: Bhupinder
authors.initials: B
authors.lastname: Singh
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014.
authors.forename: Anterpreet
authors.initials: A
authors.lastname: Kaur
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014.
authors.forename: Shashi
authors.initials: S
authors.lastname: Dhiman
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014.
authors.forename: Babita
authors.initials: B
authors.lastname: Garg
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014.
authors.forename: Rajneet Kaur
authors.initials: RK
authors.lastname: Khurana
authors.affiliation: University Institute of Pharmaceutical Sciences, UGC Centre of Advanced Studies, Panjab University, Chandigarh, India, 160 014.
authors.forename: Sarwar
authors.initials: S
authors.lastname: Beg
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000737:chemistry*; D000464:Alginates / Q000737:chemistry; D000818:Animals; D001702:Biopharmaceutics / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D005079:Excipients / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism*; D020723:Glucuronic Acid / Q000737:chemistry; D006603:Hexuronic Acids / Q000737:chemistry; D006801:Humans; D010349:Patient Compliance; D011135:Polysaccharides, Bacterial / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000464:Alginates; D003692:Delayed-Action Preparations; D005079:Excipients; D006603:Hexuronic Acids; D011135:Polysaccharides, Bacterial; C048288:gellan gum; D020723:Glucuronic Acid; D000212:Acyclovir
keywords: controlled release; gastroretention; in situ gelling; quality by design (QbD); smart polymers