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. 2015 Dec;16(6):1299-306.
doi: 10.1208/s12249-015-0314-0. Epub 2015 Mar 17.

Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation

Karine Fabio  1 , Kieran Curley  2 , Joseph Guarneri  2 , Benoit Adamo  2 , Brendan Laurenzi  2 , Marshall Grant  2 , Robin Offord  3 , Kelly Kraft  2 , Andrea Leone-Bay  2
Affiliations

Heat-Stable Dry Powder Oxytocin Formulations for Delivery by Oral Inhalation

Karine Fabio et al. AAPS PharmSciTech. 2015 Dec.

Abstract

In this work, heat stable dry powders of oxytocin (OT) suitable for delivery by oral inhalation were prepared. The OT dry powders were prepared by spray drying using excipients chosen to promote OT stability including trehalose, isoleucine, polyvinylpyrrolidone, citrate (sodium citrate and citric acid), and zinc salts (zinc chloride and zinc citrate). Characterization by laser diffraction indicated that the OT dry powders had a median particle size of 2 μm, making them suitable for delivery by inhalation. Aerodynamic performance upon discharge from proprietary dry powder inhalers was evaluated by Andersen cascade impaction (ACI) and in an anatomically correct airway (ACA) model, and confirmed that the powders had excellent aerodynamic performance, with respirable fractions up to 77% (ACI, 30 L/min). Physicochemical characterization demonstrated that the powders were amorphous (X-ray diffraction) with high glass transition temperature (modulated differential scanning calorimetry, MDSC), suggesting the potential for stabilization of the OT in a glassy amorphous matrix. OT assay and impurity profile were conducted by reverse phase HPLC and liquid chromatography-mass spectrometry (LC-MS) after storage up to 32 weeks at 40°C/75%RH. Analysis demonstrated that OT dry powders containing a mixture of citrate and zinc salts retained more than 90% of initial assay after 32 weeks storage and showed significant reduction in dimers and trisulfide formation (up to threefold reduction compared to control).

Keywords: dry powder; oral inhalation; oxytocin; peptide delivery; postpartum hemorrhage.

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Figures

Fig. 1
Fig. 1
Representative SEM images of OT spray-dried powders
Fig. 2
Fig. 2
Stability results for oxytocin powders at 40°C/75%RH
Fig. 3
Fig. 3
HPLC chromatograms of an oxytocin standard solution overlaid with Powder G after 32 weeks at 40°/75% RH. Peak labels: OT oxytocin, 1 glucose adduct, 2 deamidation product, 3 trisulfide, 4 dimer, 5 dimer
Fig. 4
Fig. 4
Degradation products (area%) in OT formulations after 32 weeks at 40°C/75% RH as determined by HPLC
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References

    1. Dept. of Reproductive Health and Research, WHO WHO recommendations for the prevention and treatment of postpartum hemorrhage; 2012.
    1. Guastella AJ, Hickie IB, McGuinness MM, et al. Recommendations for the standardisation of oxytocin nasal administration and guidelines for its reporting in human research. Psychoneuroendocrinology. 2013;38(5):612–25. doi: 10.1016/j.psyneuen.2012.11.019. - DOI - PubMed
    1. Hogerzeil HV, Walker GJA, de Goeje MJ. Stability of injectable oxytocics in tropical climates. WHOreportWHO/DAP/93.6;1993.
    1. Groot ANJA, Vree TB, Hogerzeil HV, Walker GJA. Stability of oral oxytocics in tropical climates: Results of simulation studies on oral ergometrine, oral ethylergometrine, buccal oxytocin and buccal desamino-oxytocin. Geneva: World Health Organization; 1997.
    1. Prankerd RJ, Nguyen T-H, Ibrahim JP, et al. Pulmonary delivery of an ultra-fine oxytocin dry powder formulation: potential for treatment of postpartum hemorrhage in developing countries. PLoS ONE. 2013;8(12):e82965. doi: 10.1371/journal.pone.0082965. - DOI - PMC - PubMed