In-situ forming implants for the treatment of periodontal diseases: Simultaneous controlled release of an antiseptic and an anti-inflammatory drug

[Display omitted] Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP)...

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Bibliographic Details
Published in:International journal of pharmaceutics 2019-12, Vol.572, p.118833, Article 118833
Main Authors: Lizambard, M., Menu, T., Fossart, M., Bassand, C., Agossa, K., Huck, O., Neut, C., Siepmann, F.
Format: Article
Language:English
Subjects:
Adhesiveness
Anti-Infective Agents, Local - administration & dosage
Anti-Infective Agents, Local - chemistry
Anti-Inflammatory Agents, Non-Steroidal - administration & dosage
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Bacteriology
Bioengineering
Biomaterials
Chemistry, Pharmaceutical
Chlorhexidine
Chlorhexidine - administration & dosage
Chlorhexidine - chemistry
Delayed-Action Preparations
Drug Combinations
Drug Implants
Drug Liberation
Excipients - chemistry
Galenic pharmacology
Human health and pathology
Ibuprofen
Ibuprofen - administration & dosage
Ibuprofen - chemistry
In-situ forming implants
Infectious diseases
Life Sciences
Medication
Microbiology and Parasitology
Periodontal Diseases - drug therapy
Periodontitis
Pharmaceutical sciences
Pharmacology
Plasticizers - chemistry
PLGA
Polylactic Acid-Polyglycolic Acid Copolymer - chemistry
Porosity
Solubility
Solvents - chemistry
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Summary:[Display omitted] Different types of in-situ forming implants based on poly(lactic-co-glycolic acid) (PLGA) for the controlled dual release of an antiseptic drug (chlorhexidine) and an anti-inflammatory drug (ibuprofen) were prepared and thoroughly characterized in vitro. N-methyl-pyrrolidone (NMP) was used as water-miscible solvent, acetyltributyl citrate (ATBC) as plasticizer and hydroxypropyl methylcellulose (HPMC) was added to enhance the implants’ stickiness/bioadhesion upon formation within the periodontal pocket. Different drug forms exhibiting substantially different solubilities were used: chlorhexidine dihydrochloride and digluconate as well as ibuprofen free acid and lysinate. The initial drug loadings were varied from 1.5 to 16.1%. In vitro drug release, dynamic changes in the pH of the surrounding bulk fluid and in the systems’ wet mass as well as polymer degradation were monitored. Importantly, the release of both drugs, chlorhexidine and ibuprofen, could effectively be controlled simultaneously during several weeks. Interestingly, the tremendous differences in the drug forms’ solubilities (e.g., factor >5000) did not translate into major differences in the resulting release kinetics. In the case of ibuprofen, this can likely (at least in part) be attributed to significant drug-polymer interactions (ibuprofen acts as a plasticizer for PLGA). In the case of chlorhexidine, the release of the much less soluble dihydrochloride was even faster compared to the more soluble digluconate (when combined with ibuprofen free acid). In the case of ibuprofen, at higher initial drug loadings also limited solubility effects within the implants seem to play a role, in contrast to chlorhexidine. In the latter case, instead, increased system porosity effects likely dominate at higher drug loadings.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2019.118833