title: The influence of HPMC concentration on release of theophylline or hydrocortisone from extended release mini-tablets.
abstract: BACKGROUND
  Mini-tablets are compact dosage forms, typically 2-3 mm in diameter, which have potential advantages for paediatric drug delivery. Extended release (ER) oral dosage forms are intended to release drugs continuously at rates that are sufficiently controlled to provide periods of prolonged therapeutic action following each administration, and polymers such as hypromelllose (HPMC) are commonly used to produce ER hydrophilic matrices.
  
  
  OBJECTIVE
  To develop ER mini-tablets of different sizes for paediatric delivery and to study the effects of HPMC concentration, tablet diameter and drug solubility on release rate.
  
  
  METHODS
  The solubility of Hydrocortisone and theophylline was determined. Mini-tablets (2 and 3 mm) and tablets (4 and 7 mm) comprising theophylline or hydrocortisone and HPMC (METHOCEL™ K15M) at different concentrations (30, 40, 50 and 60%w/w) were formulated. The effect of tablet size, HPMC concentration and drug solubility on release rate and tensile strength was studied.
  
  
  CONCLUSIONS
  Increasing the HPMC content and tablet diameter resulted in a significant decrease in drug release rate from ER mini-tablets. In addition, tablets and mini-tablets containing theophylline produced faster drug dissolution than those containing hydrocortisone, illustrating the influence of drug solubility on release from ER matrices. The results indicate that different drug release profiles and doses can be obtained by varying the polymer content and mini-tablet diameter, thus allowing dose flexibility to suit paediatric requirements.
  
  
  CONCLUSIONS
  This work has demonstrated the feasibility of producing ER mini-tablets to sustain drug release rate, thus allowing dose flexibility for paediatric patients. Drug release rate may be tailored by altering the mini-tablet size or the level of HPMC, without compromising tablet strength.
authors.affiliation: School of Pharmacy & Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK.
authors.forename: Faiezah A A
authors.initials: FA
authors.lastname: Mohamed
authors.forename: Matthew
authors.initials: M
authors.lastname: Roberts
authors.forename: Linda
authors.initials: L
authors.lastname: Seton
authors.forename: James L
authors.initials: JL
authors.lastname: Ford
authors.forename: Marina
authors.initials: M
authors.lastname: Levina
authors.forename: Ali R
authors.initials: AR
authors.lastname: Rajabi-Siahboomi
mesh_terms: D003692:Delayed-Action Preparations; D006854:Hydrocortisone / Q000008:administration & dosage* / Q000737:chemistry; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D012995:Solubility; D013607:Tablets; D013718:Tensile Strength; D013806:Theophylline / Q000008:administration & dosage* / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D013607:Tablets; D065347:Hypromellose Derivatives; D008747:Methylcellulose; C584694:hypromellose 2208 (100 MPA.S); D013806:Theophylline; D006854:Hydrocortisone; C584697:hypromellose 2208 (15000 MPA.S)