Effect of Polymer Permeability and Solvent Removal Rate on In Situ Forming Implants: Drug Burst Release and Microstructure

To explore the mechanism of drug release and depot formation of in situ forming implants (ISFIs), osthole-loaded ISFIs were prepared by dissolving polylactide, poly(lactide-co-glycolide), polycaprolactone, or poly(trimethylene carbonate) in different organic solvents, including N-methyl-2-pyrrolidone (NMP), dimethyl sulfoxide (DMSO), and triacetin (TA). Drug release, polymer degradation, solvent removal rate and depot microstructure were examined. The burst release effect could be reduced by using solvents exhibit slow forming phase inversion and less permeable polymers. Both the drug burst release and polymer depot microstructure were closely related to the removal rate of organic solvent. Polymers with higher permeability often displayed faster drug and solvent diffusion rates. Due to high polymer-solvent affinity, some of the organic solvent remained in the depot even after the implant was completely formed. The residual of organic solvent could be predicted by solubility parameters. The ISFI showed a lower initial release in vivo than that in vitro. In summary, the effects of different polymers and solvents on drug release and depot formation in ISFI systems were extensively investigated and discussed in this article. The two main factors, polymer permeability and solvent removal rate, were involved in different stages of drug release and depot formation in ISFI systems.

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Long-lasting in situ forming Implant loaded with Bupivacaine: Investigation on the Polymeric and Non-polymeric Carrier and Solvent Effect

Current Drug Delivery ◽

10.2174/1567201818666210617102634 ◽

2021 ◽

Vol 18 ◽

Author(s):

Saeed Bazraee ◽

Hamid Mobedi ◽

Arezuo Mashak ◽

Ahmad Jamshidi

Keyword(s):

Drug Release ◽

In Vitro Release ◽

Fickian Diffusion ◽

Morphological Properties ◽

Burst Release ◽

Solvent Concentration ◽

Drug Release Profile ◽

In Situ Forming

Introduction: Typically, in situ forming implants utilize Poly (lactide-co-glycolide) (PLGA) as a carrier and N-methyl-2-pyrrolidone (NMP) as a solvent. However, it is essential to develop different carriers to release various drugs in a controlled and sustained manner with economic and safety considerations. Objective: The present study aims to evaluate the in-vitro release of Bupivacaine HCl from in situ forming systems as post-operative local anesthesia. Methods: We used Sucrose acetate isobutyrate (SAIB), PLGA 50:50, and a mixture of them as carriers to compare the release behavior. Besides, the effect of PLGA molecular weight (RG 502H, RG 503H, and RG 504H), solvent type, and solvent concentration on the drug release profile was evaluated. The formulations were characterized by investigating their in-vitro drug release, rheological properties, solubility, and DSC, in addition to their morphological properties. Furthermore, the Korsmeyer-Peppas and Weibull models were applied to the experimental data. The results revealed that a mixture of SAIB and PLGA compared to using them solely can extend the Bupivacaine HCl release from 3 days to two weeks. Results: The DSC results demonstrated the compatibility of the mixture by showing a single Tg. The formulation with NMP had a higher burst release and final release in comparison with other solvents by 30% and 96%, respectively. Increasing the solvent concentration from 12% to 32% raised the drug release significantly, which confirmed the larger porosity in the morphology results. From the Korsmeyer-Peppas model, the mechanism of drug release is predicted to be non-Fickian diffusion.

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Effect of implant formation on drug release kinetics of in situ forming implants

International Journal of Pharmaceutics ◽

10.1016/j.ijpharm.2020.120105 ◽

2021 ◽

Vol 592 ◽

pp. 120105

Author(s):

Min Sung Suh ◽

Michail Kastellorizios ◽

Namita Tipnis ◽

Yuan Zou ◽

Yan Wang ◽

...

Keyword(s):

Drug Release ◽

Release Kinetics ◽

Drug Release Kinetics ◽

In Situ Forming ◽

Kinetics Of ◽

In Situ Forming Implants

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Drug Release from In Situ Forming Implants and Advances in Release Testing

Advanced Drug Delivery Reviews ◽

10.1016/j.addr.2021.113912 ◽

2021 ◽

pp. 113912

Author(s):

Xiaoyi Wang ◽

Diane J. Burgess

Keyword(s):

Drug Release ◽

In Situ Forming ◽

Release Testing ◽

In Situ Forming Implants

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Effect of Solvent Diffusion from In Situ-Forming Implants on Drug Release

10.26226/morressier.57d6b2b9d462b8028d88db9e ◽

2016 ◽

Author(s):

Min Sung Suh

Keyword(s):

Drug Release ◽

Solvent Diffusion ◽

Effect Of Solvent ◽

In Situ Forming ◽

In Situ Forming Implants

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Injectable in-situ Forming Depot Of Doxycycline Hyclate/α-Cyclodextrin Complex using PLGA for Periodontitis Treatment: Preparation, Charac-terization, and In-Vitro Evaluation

Current Drug Delivery ◽

10.2174/1567201817999201103195104 ◽

2020 ◽

Vol 17 ◽

Author(s):

Elham Khodaverdi ◽

Farhad Eisvand ◽

Mohammad Sina Nezami ◽

Seyedeh Nesa Rezaeian Shiadeh ◽

Hossein Kamali ◽

...

Keyword(s):

Complex Form ◽

Docking Studies ◽

Morphological Properties ◽

Burst Release ◽

Cyclodextrin Complex ◽

Doxycycline Hyclate ◽

Scanning Calorimetry ◽

In Situ Forming

Background:: Doxycycline (DOX) is used in treating a bacterial infection, especially for periodontitis treatment. Objective: To reduce irritation of DOX for subgingival administration and increase the chemical stability and against enzy-matic, the complex of α-cyclodextrin with DOX was prepared and loaded into injectable in situ forming implant based on PLGA. Methods:: FTIR, molecular docking studies, X-ray diffraction, and differential scanning calorimetry was performed to char-acterize the DOX/α-cyclodextrin complex. Finally, the in-vitro drug release and modeling, morphological properties, and cellular cytotoxic effects were also evaluated. Results:: The stability of DOX was improved with complex than pure DOX. The main advantage of the complex is the al-most complete release (96.31 ± 2.56 %) of the drug within 14 days of the implant, whereas in the formulation containing the pure DOX and the physical mixture the DOX with α-cyclodextrin release is reached to 70.18 ± 3.61 % and 77.03 ± 3.56 %, respectively. This trend is due to elevate of DOX stability in the DOX/ α-cyclodextrin complex form within PLGA implant that confirmed by the results of stability. Conclusion:: Our results were indicative that the formulation containing DOX/α-cyclodextrin complex was biocompatible and sustained-release with minimum initial burst release.

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Poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) Copolymers for the Formulation of In Situ Forming Depot Long-Acting Injectables

Pharmaceutics ◽

10.3390/pharmaceutics13050605 ◽

2021 ◽

Vol 13 (5) ◽

pp. 605

Author(s):

Marie-Emérentienne Cagnon ◽

Silvio Curia ◽

Juliette Serindoux ◽

Jean-Manuel Cros ◽

Feifei Ng ◽

...

Keyword(s):

Ethylene Glycol ◽

Surface Erosion ◽

Sustained Delivery ◽

Trimethylene Carbonate ◽

Poly Ethylene Glycol ◽

In Situ Forming ◽

Poly Ethylene ◽

Long Acting

This article describes the utilization of (methoxy)poly(ethylene glycol)-b-poly(1,3-trimethylene carbonate) ((m)PEG–PTMC) diblock and triblock copolymers for the formulation of in situ forming depot long-acting injectables by solvent exchange. The results shown in this manuscript demonstrate that it is possible to achieve long-term drug deliveries from suspension formulations prepared with these copolymers, with release durations up to several months in vitro. The utilization of copolymers with different PEG and PTMC molecular weights affords to modulate the release profile and duration. A pharmacokinetic study in rats with meloxicam confirmed the feasibility of achieving at least 28 days of sustained delivery by using this technology while showing good local tolerability in the subcutaneous environment. The characterization of the depots at the end of the in vivo study suggests that the rapid phase exchange upon administration and the surface erosion of the resulting depots are driving the delivery kinetics from suspension formulations. Due to the widely accepted utilization of meloxicam as an analgesic drug for animal care, the results shown in this article are of special interest for the development of veterinary products aiming at a very long-term sustained delivery of this therapeutic molecule.

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