Aqueous stability of leuprolide acetate: effect of temperature, dissolved oxygen, pH and complexation with β-cyclodextrin

Rahimi, Mehdi; Mobedi, Hamid; Behnamghader, Aliasghar

doi:10.3109/10837450.2014.971377

Cited by 10 publications

(4 citation statements)

References 61 publications

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“…Additionally, it is crucial to handle the peptides gently and avoid agitation or shear stress, as these can cause structural damage and increase their susceptibility to oxidation [ 157 ]. The effect of temperature on oxygen solubility also needs to be considered during processing because dissolved oxygen concentrations at low temperatures is higher in an aqueous solution [ 158 ].…”

Section: Strategies To Optimize Peptide Stability In Aqueous Formulat...mentioning

confidence: 99%

Designing Formulation Strategies for Enhanced Stability of Therapeutic Peptides in Aqueous Solutions: A Review

et al. 2023

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Over the past few decades, there has been a tremendous increase in the utilization of therapeutic peptides. Therapeutic peptides are usually administered via the parenteral route, requiring an aqueous formulation. Unfortunately, peptides are often unstable in aqueous solutions, affecting stability and bioactivity. Although a stable and dry formulation for reconstitution might be designed, from a pharmaco-economic and practical convenience point of view, a peptide formulation in an aqueous liquid form is preferred. Designing formulation strategies that optimize peptide stability may improve bioavailability and increase therapeutic efficacy. This literature review provides an overview of various degradation pathways and formulation strategies to stabilize therapeutic peptides in aqueous solutions. First, we introduce the major peptide stability issues in liquid formulations and the degradation mechanisms. Then, we present a variety of known strategies to inhibit or slow down peptide degradation. Overall, the most practical approaches to peptide stabilization are pH optimization and selecting the appropriate type of buffer. Other practical strategies to reduce peptide degradation rates in solution are the application of co-solvency, air exclusion, viscosity enhancement, PEGylation, and using polyol excipients.

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Section: Strategies To Optimize Peptide Stability In Aqueous Formulat...mentioning

confidence: 99%

Designing Formulation Strategies for Enhanced Stability of Therapeutic Peptides in Aqueous Solutions: A Review

et al. 2023

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“…Ito et al reported that microneedles based on sodium chondroitin sulfate improved skin stability by protecting LA degradation, resulting in increased the relative bioavailability [10]. Rahimi et al have reported that improvement of LA stability by making complex with ß-cyclodextrin at various pH values (2.0-7.4) [11].…”

Section: Introductionmentioning

confidence: 99%

Development of Self-Administered Formulation to Improve the Bioavailability of Leuprorelin Acetate

et al. 2022

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In recent years, the development of self-injectable formulations has attracted much attention, and the development of formulations to control pharmacokinetics, as well as drug release and migration in the skin, has become an active research area. In the present study, the development of a lipid-based depot formulation containing leuprorelin acetate (LA) as an easily metabolizable drug in the skin was prepared with a novel non-lamellar liquid-crystal-forming lipid of mono-O-(5,9,13-trimethyl-4-tetradecenyl) glycerol ester (MGE). Small-angle X-ray scattering, cryo-transmission electron microscopy, and nuclear magnetic resonance observations showed that the MGE-containing formulations had a face-centered cubic packed micellar structure. In addition, the bioavailability (BA) of LA after subcutaneous injection was significantly improved with the MGE-containing formulation compared with the administration of LA solution. Notably, higher Cmax and faster Tmax were obtained with the MGE-containing formulation, and the BA increased with increasing MGE content in the formulation, suggesting that LA migration into the systemic circulation and its stability might be enhanced by MGE. These results may support the development of self-administered formulations of peptide drugs as well as nucleic acids, which are easily metabolized in the skin.

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“…15,16 Cyclodextrins have been used in pharmaceutical formulation to enhance the stability or to modulate the biological activity of drugs over wide pH ranges. 17 The use of cyclodextrin to increase the physical and chemical stability or compounds in solution and in other forms has been well documented in the literature. 18 Cyclodextrins have also been used to overcome other issues, such as a bitter taste in foods and the controlled release of drugs for oral and parenteral delivery.…”

Section: ■ Introductionmentioning

confidence: 99%

“…The acceptable daily intake (ADI) of αCD was determined as “not specified” by The Joint FAO/WHO Expert Committee on Food Additives. Numerous reviews have been published regarding the use of cyclodextrins in oral-dosage forms, many of which have specifically addressed the effects of cyclodextrins on oral absorption and/or bioavailability. , Cyclodextrins have been used in pharmaceutical formulation to enhance the stability or to modulate the biological activity of drugs over wide pH ranges …”

Section: Introductionmentioning

confidence: 99%

Administration of Piceatannol Complexed with α-Cyclodextrin Improves Its Absorption in Rats

Inagaki

Ito

Setoguchi

et al. 2016

J. Agric. Food Chem.

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Piceatannol is polyphenolic antioxidant found in passion fruit (Passiflora edulis) seeds. The aim of this study was to improve the absorption of piceatannol using α-cyclodextrin (αCD). The solubility of piceatannol in neutral and acidic solutions increased in an αCD concentration-dependent manner. The maximum plasma concentration of intact piceatannol and the time-to-maximum plasma concentration of O-methylated piceatannol metabolites increased in rats administered αCD-piceatannol inclusion complexes (PICs). Administering the αCD inclusion complexes significantly increased the area under the concentration-time curve of total stilbene derivatives (0-3 h) in terms of the total amount of intact piceatannol, O-methylated piceatannol, conjugated piceatannol, and isorhapontigenin. Gastrointestinal ligation experiments demonstrated that substantially higher levels of piceatannol metabolites were present in the lower intestine (the ileum) at 1 h postintragastric αCD-PICs administration as compared to those observed following piceatannol administration only. These results suggested that αCD enhanced piceatannol movement and absorption in the small intestine.

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Aqueous stability of leuprolide acetate: effect of temperature, dissolved oxygen, pH and complexation with β-cyclodextrin

Cited by 10 publications

References 61 publications

Designing Formulation Strategies for Enhanced Stability of Therapeutic Peptides in Aqueous Solutions: A Review

Designing Formulation Strategies for Enhanced Stability of Therapeutic Peptides in Aqueous Solutions: A Review

Development of Self-Administered Formulation to Improve the Bioavailability of Leuprorelin Acetate

Administration of Piceatannol Complexed with α-Cyclodextrin Improves Its Absorption in Rats

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