Quality by design approach to optimize the formulation variables influencing the characteristics of biodegradable intramuscular in-situ gel loaded with alendronate sodium for osteoporosis

Autor: Waleed Yousof Rizg, Khaled M. Hosny
Rok vydání: 2018
Předmět:
Polymers
Chemistry
Pharmaceutical
lcsh:Medicine
02 engineering and technology
Physical Chemistry
030226 pharmacology & pharmacy
chemistry.chemical_compound
0302 clinical medicine
Pulmonary surfactant
Materials Physics
Medicine and Health Sciences
lcsh:Science
Connective Tissue Diseases
Routes of Administration
Drug Carriers
Multidisciplinary
Alendronate
Viscosity
Pharmaceutics
Chemistry
Physics
Experimental Design
021001 nanoscience & nanotechnology
Controlled release
Macromolecules
Research Design
Physical Sciences
Polycaprolactone
Drug delivery
Rabbits
0210 nano-technology
Research Article
Drug Administration
Materials by Structure
Polyesters
Materials Science
Biological Availability
Research and Analysis Methods
03 medical and health sciences
Rheumatology
Drug Therapy
Pharmacokinetics
Animals
Humans
Intramuscular Injections
Pharmacology
Chromatography
lcsh:R
Biodegradation
Polymer Chemistry
Rats
Bioavailability
Alendronate Sodium
Chemical Properties
Delayed-Action Preparations
Osteoporosis
lcsh:Q
Drug Delivery
Gels
Zdroj: PLoS ONE
PLoS ONE, Vol 13, Iss 6, p e0197540 (2018)
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0197540
Popis: There are many challenges facing the use of alendronate sodium for the treatment of osteoporosis such as low bioavailability of 0.6% and oesophageal ulceration with bleeding. Due to the aforementioned limitation, the main objective of this research is to utilize a statistical experimental design in the formulation and optimization of alendronate in the form of controlled release biodegradable intramuscular in-situ gel. A Box-Behnken experimental design employing Statgraphics® software was used to develop an optimized in-situ gel formulation and to estimate the effects of Poly-DL-lactide-coglycolide as a primary polymer, the copolymer polycaprolactone, and lipid surfactant capryol 90. Every system was evaluated for gellation character, and in vitro release. As a novel technique for evaluation of the in-situ gel, in-vivo biodegradability rate was estimated in rats. Pharmacokinetic parameters were assessed in rabbits. The results indicated a significant effect of the copolymer and lipid surfactant on initial burst, and a significant effect of the primary and copolymer on drug percentage released. The optimum formulation showed a 5% initial burst, an in-vivo biodegradability rate estimated at 8% every seven days in rats, and the pharmacokinetic evaluation revealed that alendronate sodium mean residence time extended to 102 days in rabbits. In conclusion, the optimum biodegradable intramuscular in-situ gel formulations is a promising approach for providing higher bioavailability, extended release for more than three months, with elimination of esophageal side effects.
Databáze: OpenAIRE
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