title: Melt-in-Mouth Multi-particulate System for the Treatment of ADHD: A Convenient Platform for Pediatric Use.
abstract: Generally, pellets obtained from extrusion/spheronization, containing microcrystalline cellulose (MCC), do not disintegrate. An attempt has been made to develop melt-in-mouth pellets of taste-masked atomoxetine hydrochloride, using extrusion-spheronization, for pediatric patients. Melt-in-mouth pellets were prepared using extrusion-spheronization method and optimized using 3(3) FFD. MCC (X1, %), mannitol (X2, %) and Indion 414: Pharmaburst 500 ratio (X3, ratio) were the factors (independent variables) studied, whereas responses studied (dependent variables) were friability (Y1, %), yield (Y2, %) shape (Y3, roundness) in vitro disintegration time (Y4, seconds). The optimized formulation obtained from FFD was characterized for friability, shape and morphology, in vitro disintegration time, porosity, moisture uptake, in vitro release study and in vivo taste and disintegration time in healthy human volunteers. Randomized, two-treatment, two-sequence, two-period, single dose, crossover sensory evaluation study of taste-masked melt-in-mouth pellet was carried out in 10 healthy human subjects. A statistically significant polynomial mathematical relationship was generated between the factors and responses to obtain an optimized formulation. The optimized formulation was characterized (in vitro and in vivo) and exhibited a rapid drug release in vitro attributed to fast disintegration of pellets and high solubility of drug in 0.1 N HCl and buffer (pH 6.8). In vivo, 40% of volunteers ranked taste-masked optimized formulation as slightly bitter while 60% ranked it as no taste. The optimized pellets were conveniently administered in volunteers and exhibited rapid in-vivo disintegration in the oral cavity. Melt-in-mouth pellets can be a used as a platform technology for administering drugs to paediatric patients accurately and conveniently resulting in patient compliance.
authors.affiliation: Department of Pharmaceutics, NIPER Ahmedabad, Ahmedabad, 380054, India.
authors.forename: Jalashri
authors.initials: J
authors.lastname: Patadia
authors.affiliation: Department of Pharmaceutics, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, India.|Adjunct faculty, Department of Pharmaceutics, NIPER Ahmedabad, C/o B.V. Patel PERD Centre, S.G. Highway, Thaltej, Ahmedabad, Gujarat, 380054, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Tripathi
authors.affiliation: Department of Pharmaceutics, B. V. Patel Pharmaceutical Education and Research Development (PERD) Centre, Ahmedabad, 380054, India. amitagarg4@gmail.com.|Adjunct faculty, Department of Pharmaceutics, NIPER Ahmedabad, C/o B.V. Patel PERD Centre, S.G. Highway, Thaltej, Ahmedabad, Gujarat, 380054, India. amitagarg4@gmail.com.
authors.forename: Amita
authors.initials: A
authors.lastname: Joshi
mesh_terms: D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000188:drug therapy*; D002482:Cellulose / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D018592:Cross-Over Studies; D004343:Drug Implants / Q000008:administration & dosage* / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry; D005260:Female; D006801:Humans; D008297:Male; D008353:Mannitol / Q000737:chemistry; D009055:Mouth / Q000378:metabolism*; D010372:Pediatrics; D011109:Polymethacrylic Acids / Q000737:chemistry; D012995:Solubility; D013649:Taste / Q000187:drug effects
chemical_list: D004343:Drug Implants; D005079:Excipients; D011109:Polymethacrylic Acids; D008353:Mannitol; C012553:spherons; D002482:Cellulose; C109691:microcrystalline cellulose
keywords: full factorial design; oro-dispersible; pediatric; pellets; quality by design (QbD); taste masking