Subcutaneous administration of the retrograde transport inhibitor Retro-2.1 formulated in a PLGA-PEG-PLGA thermosensitive hydrogel leads to a sustained release of the drug and a better control of its metabolism in vivo

AbstractThe GLP-1 class of peptide agonists has been shown to exert regulatory key roles in both diabetes, obesity and related complications. Given the short half-life of GLP-1 its use has been historically discouraged. We developed polymeric microparticles loaded with either human GLP-1 (7-37) or liraglutide peptides by double emulsion and solvent evaporation approach. The size distribution of all formulations was of about 30-50 μm. The in vitro kinetic release assays showed a sustained release of the peptides extending up to 30 to 40 days with varying profiles. Morphologic analysis demonstrated a more regular particle surface for those comprising polymers PLA, PLA-PEG and PLGA. In vivo evaluation in Swiss male mice demonstrated a similar extension of effect of decreasing in body weight gain for up to 25 days after a single subcutaneous administration of either hGLP-1 or liraglutide peptide-loaded microparticles (200 μg peptide / kg body weight) compared to controls. These demonstrate the effectiveness of hGLP-1 as a therapeutic agent in long-term, continuous release from peptide-load microparticles, and thus its plausibility as an unmodified therapeutic agent.

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Formulation and Evaluation of Itopride Hydrochloride Floating Beads for Gastroretentive Delivery

International Journal of Pharmaceutical Sciences and Nanotechnology ◽

10.37285/ijpsn.2013.6.4.10 ◽

2013 ◽

Vol 6 (4) ◽

pp. 2269-2280

Author(s):

Nagratna Dhople ◽

P N Dandag ◽

A P Gadad ◽

C K Pandey ◽

Masthiholimath V S

Keyword(s):

Sustained Release ◽

In Vitro Release ◽

Entrapment Efficiency ◽

Sustained Release Formulation ◽

Prokinetic Drug ◽

Drug Entrapment Efficiency ◽

Itopride Hydrochloride ◽

Vitro Release

A gastroretentive sustained release system of itopride hydrochloride was formulated to increase the gastric residence time and modulate its release behavior. Itopride hydrochloride is a prokinetic drug used in the treatment of gastroeosophageal reflux disease, Non-ulcer dyspepsia and as an antiemetic. Hence, itopride hydrochloride beads were prepared by emulsion gelation method by employing low methoxy pectin and sodium alginate as sustained release polymers in three different ratios alone and in combination and sunflower oil was used to enable floating property to the beads. The effect of variation in polymer and their concentration was investigated. The beads were evaluated for production yield, particle size, swelling index, density measurement, buoyancy, drug content, drug entrapment efficiency, in vitro release characteristics and release kinetic study. Based on drug entrapment efficiency, buoyancy, swelling and in vitro release, F9 was selected as the optimized formulation. F9 was further subjected to surface morphology by SEM, in vitro release comparison with marketed formulation, in vivo floating study in rabbits and stability study for 90 days. In vitro release follows zero order and fitted in Korsmeyer peppas model (Non-Fickian release). Therefore, the rate of drug release is due to the combined effect of drug diffusion and polymer swelling. The in vivo X-ray studies revealed that the beads were floating in the rabbit stomach up to 10 hours. Thus, it was concluded that the sustained release formulation containing itopride hydrochloride was found to improve patient compliance, minimize the side effects and decrease the frequency of administration.

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Formulation and Evaluation of Atorvastatin Calcium-Poly-ε-Caprolactone Nanoparticles Loaded Ocular Inserts for Sustained Release and Antiinflammatory Efficacy

Current Pharmaceutical Biotechnology ◽

10.2174/1389201021666200519133350 ◽

2020 ◽

Vol 21 (15) ◽

pp. 1688-1698

Author(s):

Germeen N.S. Girgis

Keyword(s):

Sustained Release ◽

In Vitro Release ◽

Pluronic F127 ◽

In Vivo Study ◽

Average Weight ◽

Drug Release Profile ◽

Atorvastatin Calcium ◽

Anti Inflammatory

Purpose: The work was performed to investigate the feasibility of preparing ocular inserts loaded with Poly-ε-Caprolactone (PCL) nanoparticles as a sustained ocular delivery system. Methods: First, Atorvastatin Calcium-Poly-ε-Caprolactone (ATC-PCL) nanoparticles were prepared and characterized. Then, the optimized nanoparticles were loaded within inserts formulated with Methylcellulose (MC) and Polyvinyl Alcohol (PVA) by a solvent casting technique and evaluated physically, for in-vitro drug release profile. Finally, an in-vivo study was performed on the selected formulation to prove non-irritability and sustained ocular anti-inflammatory efficacy compared with free drug-loaded ocuserts. Results: The results revealed (ATC-PCL) nanoparticles prepared with 0.5% pluronic F127 were optimized with 181.72±3.6 nm particle size, 0.12±0.02 (PDI) analysis, -27.4± 0.69 mV zeta potential and 62.41%±4.7% entrapment efficiency. Nanoparticles loaded ocuserts manifested compatibility between drug and formulation polymers. Moreover, formulations complied with average weight 0.055±0.002 to 0.143±0.023 mg, and accepted pH. ATC-PCL nanoparticles loaded inserts prepared by 5% MC showed more sustained, prolonged in-vitro release over 24h. In-vivo study emphasized non-irritability, ocular anti-inflammatory effectiveness represented by smaller lid closure scores, and statistically significant lowering in PMN count after 3h. Conclusion: These findings proposed a possibly simple, new and affordable price technique to prepare promising (ATC-PCL) nanoparticles loaded inserts to achieve sustained release with prolonged antiinflammatory efficacy.

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Development and In Vitro-In Vivo Evaluation of a Novel Sustained-Release Loxoprofen Pellet with Double Coating Layer

Pharmaceutics ◽

10.3390/pharmaceutics11060260 ◽

2019 ◽

Vol 11 (6) ◽

pp. 260 ◽

Cited By ~ 4

Author(s):

Dongwei Wan ◽

Min Zhao ◽

Jingjing Zhang ◽

Libiao Luan

Keyword(s):

Citric Acid ◽

Drug Release ◽

Sustained Release ◽

Release Rate ◽

Diffusion Rate ◽

Immediate Release ◽

Pharmacokinetic Studies ◽

Release Tablet

This study aimed to develop a novel sustained release pellet of loxoprofen sodium (LXP) by coating a dissolution-rate controlling sub-layer containing hydroxypropyl methyl cellulose (HPMC) and citric acid, and a second diffusion-rate controlling layer containing aqueous dispersion of ethyl cellulose (ADEC) on the surface of a LXP conventional pellet, and to compare its performance in vivo with an immediate release tablet (Loxinon®). A three-level, three-factor Box-Behnken design and the response surface model (RSM) were used to investigate and optimize the effects of the citric acid content in the sub-layer, the sub-layer coating level, and the outer ADEC coating level on the in vitro release profiles of LXP sustained release pellets. The pharmacokinetic studies of the optimal sustained release pellets were performed in fasted beagle dogs using an immediate release tablet as a reference. The results illustrated that both the citric acid (CA) and ADEC as the dissolution- and diffusion-rate controlling materials significantly decreased the drug release rate. The optimal formulation showed a pH-independent drug release in media at pH above 4.5 and a slightly slow release in acid medium. The pharmacokinetic studies revealed that a more stable and prolonged plasma drug concentration profile of the optimal pellets was achieved, with a relative bioavaibility of 87.16% compared with the conventional tablets. This article provided a novel concept of two-step control of the release rate of LXP, which showed a sustained release both in vitro and in vivo.

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Fabrication, characterization and in vivo evaluation of dexpanthenol sustained-release nanofibers for wound healing

Polymer Testing ◽

10.1016/j.polymertesting.2020.106827 ◽

2020 ◽

Vol 91 ◽

pp. 106827

Author(s):

Maryam Najafiasl ◽

Shahriar Osfouri ◽

Reza Azin ◽

Sasan Zaeri

Keyword(s):

Wound Healing ◽

Sustained Release ◽

In Vivo Evaluation

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Development of In Situ Self-Assembly Nanoparticles to Encapsulate Lopinavir and Ritonavir for Long-Acting Subcutaneous Injection

Pharmaceutics ◽

10.3390/pharmaceutics13060904 ◽

2021 ◽

Vol 13 (6) ◽

pp. 904

Author(s):

Irin Tanaudommongkon ◽

Asama Tanaudommongkon ◽

Xiaowei Dong

Keyword(s):

Sustained Release ◽

Trough Concentration ◽

Self Assembly ◽

Subcutaneous Injection ◽

Drug Loading ◽

Entrapment Efficiency ◽

Long Acting

Most antiretroviral medications for human immunodeficiency virus treatment and prevention require high levels of patient adherence, such that medications need to be administered daily without missing doses. Here, a long-acting subcutaneous injection of lopinavir (LPV) in combination with ritonavir (RTV) using in situ self-assembly nanoparticles (ISNPs) was developed to potentially overcome adherence barriers. The ISNP approach can improve the pharmacokinetic profiles of the drugs. The ISNPs were characterized in terms of particle size, drug entrapment efficiency, drug loading, in vitro release study, and in vivo pharmacokinetic study. LPV/RTV ISNPs were 167.8 nm in size, with a polydispersity index of less than 0.35. The entrapment efficiency was over 98% for both LPV and RTV, with drug loadings of 25% LPV and 6.3% RTV. A slow release rate of LPV was observed at about 20% on day 5, followed by a sustained release beyond 14 days. RTV released faster than LPV in the first 5 days and slower than LPV thereafter. LPV trough concentration remained above 160 ng/mL and RTV trough concentration was above 50 ng/mL after 6 days with one subcutaneous injection. Overall, the ISNP-based LPV/RTV injection showed sustained release profiles in both in vitro and in vivo studies.

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