title: A mathematical model for interpreting in vitro rhGH release from laminar implants.
abstract: Recombinant human growth hormone (rhGH), used mainly for the treatment of growth hormone deficiency in children, requires daily subcutaneous injections. The use of controlled release formulations with appropriate rhGH release kinetics reduces the frequency of medication, improving patient compliance and quality of life. Biodegradable implants are a valid alternative, offering the feasibility of a regular release rate after administering a single dose, though it exists the slight disadvantage of a very minor surgical operation. Three laminar implant formulations (F(1), F(2) and F(3)) were produced by different manufacture procedures using solvent-casting techniques with the same copoly(D,L-lactic) glycolic acid (PLGA) polymer (Mw=48 kDa). A correlation in vitro between polymer matrix degradation and drug release rate from these formulations was found and a mathematical model was developed to interpret this. This model was applied to each formulation. The obtained results where explained in terms of manufacture parameters with the aim of elucidate whether drug release only occurs by diffusion or erosion, or by a combination of both mechanisms. Controlling the manufacture method and the resultant changes in polymer structure facilitates a suitable rhGH release profile for different rhGH deficiency treatments.
authors.affiliation: Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 La Laguna, Tenerife, Spain. ansanto@ull.es
authors.forename: A
authors.initials: A
authors.lastname: Santoveña
authors.forename: J T
authors.initials: JT
authors.lastname: García
authors.forename: A
authors.initials: A
authors.lastname: Oliva
authors.forename: M
authors.initials: M
authors.lastname: Llabrés
authors.forename: J B
authors.initials: JB
authors.lastname: Fariña
mesh_terms: D001672:Biocompatible Materials / Q000737:chemistry; D004343:Drug Implants; D019382:Human Growth Hormone / Q000737:chemistry*; D066298:In Vitro Techniques; D007700:Kinetics; D019344:Lactic Acid / Q000737:chemistry; D008956:Models, Chemical; D008962:Models, Theoretical; D008970:Molecular Weight; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D004343:Drug Implants; D011108:Polymers; D011994:Recombinant Proteins; D019382:Human Growth Hormone; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid