title: Freeze-dried, mucoadhesive system for vaginal delivery of the HIV microbicide, dapivirine: optimisation by an artificial neural network.
abstract: Dapivirine mucoadhesive gels and freeze-dried tablets were prepared using a 3x3x2 factorial design. An artificial neural network (ANN) with multi-layer perception was used to investigate the effect of hydroxypropyl-methylcellulose (HPMC): polyvinylpyrrolidone (PVP) ratio (X1), mucoadhesive concentration (X2) and delivery system (gel or freeze-dried mucoadhesive tablet, X3) on response variables; cumulative release of dapivirine at 24h (Q(24)), mucoadhesive force (F(max)) and zero-rate viscosity. Optimisation was performed by minimising the error between the experimental and predicted values of responses by ANN. The method was validated using check point analysis by preparing six formulations of gels and their corresponding freeze-dried tablets randomly selected from within the design space of contour plots. Experimental and predicted values of response variables were not significantly different (p>0.05, two-sided paired t-test). For gels, Q(24) values were higher than their corresponding freeze-dried tablets. F(max) values for freeze-dried tablets were significantly different (2-4 times greater, p>0.05, two-sided paired t-test) compared to equivalent gels. Freeze-dried tablets having lower values for X1 and higher values for X2 components offered the best compromise between effective dapivirine release, mucoadhesion and viscosity such that increased vaginal residence time was likely to be achieved.
authors.affiliation: School of Pharmacy, Queen's University Belfast, Medical Biology Centre, 97 Lisburn Road, Belfast BT9 7BL, Northern Ireland, UK.
authors.forename: A David
authors.initials: AD
authors.lastname: Woolfson
authors.forename: Manish L
authors.initials: ML
authors.lastname: Umrethia
authors.forename: Victoria L
authors.initials: VL
authors.lastname: Kett
authors.forename: R Karl
authors.initials: RK
authors.lastname: Malcolm
mesh_terms: D000268:Adhesiveness; D000282:Administration, Intravaginal; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004337:Drug Carriers / Q000737:chemistry*; D005612:Freeze Drying; D005782:Gels; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D016571:Neural Networks, Computer; D011205:Povidone / Q000737:chemistry; D011743:Pyrimidines / Q000008:administration & dosage* / Q000737:chemistry; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry; D013607:Tablets
chemical_list: D004337:Drug Carriers; D005782:Gels; D011743:Pyrimidines; D018894:Reverse Transcriptase Inhibitors; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; D011205:Povidone; C481671:Dapivirine