Oxytocin formulations and uses thereof

The present invention relates to the field of preventive and therapeutic medicine, in particular to peptide formulations. Provided is a p H-buffered aqueous formulation comprising oxytocin, vasopressin or an analogue thereof and at least one non-toxic source of divalent metal ions in a concentration of at least 2 m M, and the use of the formulation for the manufacture of a medicament for therapeutic and/or prophylactic treatments. Also provided is a method for treating or preventing haemorrhage in a subject in need thereof, comprising administering to said subject an effective dosage amount of an oxytocin formulation according to the invention. Further provided is a method for treating or preventing diabetes insipidus or vasodilatory shock in a subject in need thereof, comprising administering to said subject an effective dosage amount of a vasopressin formulation according to the invention

Peptide formulations and uses thereof

The present invention relates to the field of preventive and therapeutic medicine, in particular to peptide formulations. Provided is a p H-buffered aqueous formulation comprising oxytocin, vasopressin or an analogue thereof and at least one non-toxic source of divalent metal ions in a concentration of at least 2 m M, and the use of the formulation for the manufacture of a medicament for therapeutic and/or prophylactic treatments. Also provided is a method for treating or preventing haemorrhage in a subject in need thereof, comprising administering to said subject an effective dosage amount of an oxytocin formulation according to the invention. Further provided is a method for treating or preventing diabetes insipidus or vasodilatory shock in a subject in need thereof, comprising administering to said subject an effective dosage amount of a vasopressin formulation according to the invention

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

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

UV-Vis Spectroscopy to Enable Determination of the Dissolution Behavior of Solid Dispersions Containing Curcumin and Piperine

Objective: Curcumin and piperine exibit poor aqueous solubility and dissolution. Solid dispersion technology is a promising way to improve dissolution of lipophilic compounds. Therefore, to investigate the dissolution behavior, an accurate determination of curcumin and piperine concentrations in a sample containing 0.5 wt-% SLS in sodium phosphate buffer as the dissolution medium was required. The goal of research was to investigate whether UV-Vis spectroscopy can be used to accurately determine curcumin and piperine concentrations in aqueous solutions. Method: Stock solutions (1 mg/mL) of curcumin and piperine were prepared in methanol. A series of solutions for calibration were prepared by mixing the stock solutions in various ratios after which they were diluted with dissolution medium (0.5%-wt sodium lauryl sulfate in 20 mM phosphate buffer; pH 6.0). Solutions of curcumin (2 mu g/mL) and piperine (1 mu g/mL were subjected to overlay scan in a UV-VIS spectrophotometer in each. max of 430 and 335.5 nm for curcumin and piperine, respectively. The method was validated according ICH requirements, such as specificity, linearity, accuracy, precision, limit of detection and limit of quantification. Results: At a concentration range of 0.1 to 5 mu g/mL, calibration curves of curcumin and piperine showed linearity with R-2 = 0.9980 and 0.9982, respectively. Precision and accuracy was confirmed by AOAC. Furthermore, LOD of both compounds was 0.23 mu g/mL and LOQ of curcumin and piperine was 0.72 and 0.69 mu g/mL, respectively. Conclusion: UV-Vis spectroscopy can be used to accurately determine curcumin and piperine concentrations in dissolution samples obtained during screening the dissolution behavior of solid dispersions containing these compounds

UV-Vis spectroscopy to enable determination of the dissolution behavior of solid dispersions containing curcumin and piperine

Objective: Curcumin and piperine exibit poor aqueous solubility and dissolution. Solid dispersion technology is a promising way to improve dissolution of lipophilic compounds. Therefore, to investigate the dissolution behavior, an accurate determination of curcumin and piperine concentrations in a sample containing 0.5 wt-% SLS in sodium phosphate buffer as the dissolution medium was required. The goal of research was to investigate whether UV-Vis spectroscopy can be used to accurately determine curcumin and piperine concentrations in aqueous solutions. Method: Stock solutions (1 mg/mL) of curcumin and piperine were prepared in methanol. A series of solutions for calibration were prepared by mixing the stock solutions in various ratios after which they were diluted with dissolution medium (0.5%-wt sodium lauryl sulfate in 20 mM phosphate buffer; pH 6.0). Solutions of curcumin (2 mu g/mL) and piperine (1 mu g/mL were subjected to overlay scan in a UV-VIS spectrophotometer in each. max of 430 and 335.5 nm for curcumin and piperine, respectively. The method was validated according ICH requirements, such as specificity, linearity, accuracy, precision, limit of detection and limit of quantification. Results: At a concentration range of 0.1 to 5 mu g/mL, calibration curves of curcumin and piperine showed linearity with R-2 = 0.9980 and 0.9982, respectively. Precision and accuracy was confirmed by AOAC. Furthermore, LOD of both compounds was 0.23 mu g/mL and LOQ of curcumin and piperine was 0.72 and 0.69 mu g/mL, respectively. Conclusion: UV-Vis spectroscopy can be used to accurately determine curcumin and piperine concentrations in dissolution samples obtained during screening the dissolution behavior of solid dispersions containing these compounds

Compacted Solid Dosage Form

The present invention relates to dosage forms comprising a compressed blend of a biologically active ingredient, one or more polymers like a poly(α-hydroxy carboxylic acid) in which optionally is incorporated a glass transition modifying agent, and optional further ingredients, wherein the polymer or polymeric mixture has a specific glass transition temperature which causes the system to be in the glassy state at ambient conditions before administration and to be in the rubbery state under the physiological conditions to which the system is exposed after administration, resulting in pulsed release of said biologically active ingredient

Designing CAF-adjuvanted dry powder vaccines:Spray drying preserves the adjuvant activity of CAF01

<p>Dry powder vaccine formulations are highly attractive due to improved storage stability and the possibility for particle engineering, as compared to liquid formulations. However, a prerequisite for formulating vaccines into dry formulations is that their physicochemical and adjuvant properties remain unchanged upon rehydration. Thus, we have identified and optimized the parameters of importance for the design of a spray dried powder formulation of the cationic liposomal adjuvant formulation 01 (CAF01) composed of dimethyldioctadecylammonium (DDA) bromide and trehalose 6,6'-dibehenate (TDB) via spray drying. The optimal excipient to stabilize CAF01 during spray drying and for the design of nanocomposite microparticles was identified among mannitol, lactose and trehalose. Trehalose and lactose were promising stabilizers with respect to preserving liposome size, as compared to mannitol. Trehalose and lactose were in the glassy state upon co-spray drying with the liposomes, whereas mannitol appeared crystalline, suggesting that the ability of the stabilizer to form a glassymatrix around the liposomes is one of the prerequisites for stabilization. Systematic studies on the effect of process parameters suggested that a fast drying rate is essential to avoid phase separation and lipid accumulation at the surface of the microparticles during spray drying. Finally, immunization studies in mice with CAF01 in combination with the tuberculosis antigen Ag85B-ESAT6-Rv2660c (H56) demonstrated that spray drying of CAF01 with trehalose under optimal processing conditions resulted in the preservation of the adjuvant activity in vivo. These data demonstrate the importance of liposome stabilization via optimization of formulation and processing conditions in the engineering of dry powder liposome formulations. (C) 2013 Elsevier B. V. All rights reserved.</p>