المؤلفون: Mohammad Enamul Hoque, Pete Lambert, Alison Morgan, Abbey Byrne, Michelle P. McIntosh, Natalie Carvalho, Victoria L. Oliver, Michelle Kermode

المصدر: BMC Medicine, Vol 18, Iss 1, Pp 1-18 (2020)
BMC Medicine

مصطلحات موضوعية: Adult, Respiratory Therapy, Adolescent, Cost effectiveness, Cost-Benefit Analysis, Comparative effectiveness research, Global health, Sustainable development goals, Health economic analysis, lcsh:Medicine, Oxytocin, Gross domestic product, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Environmental health, medicine, Humans, 030212 general & internal medicine, Cold chain, Misoprostol, health care economics and organizations, Bangladesh, 030219 obstetrics & reproductive medicine, Cost–benefit analysis, business.industry, Heat-stable uterotonics, Postpartum Hemorrhage, lcsh:R, General Medicine, Middle Aged, medicine.disease, Female, Maternal health, Ethiopia, business, Research Article, medicine.drug

الوصف: Background Access to oxytocin for prevention of postpartum haemorrhage (PPH) in resource-poor settings is limited by the requirement for a consistent cold chain and for a skilled attendant to administer the injection. To overcome these barriers, heat-stable, non-injectable formulations of oxytocin are under development, including oxytocin for inhalation. This study modelled the cost-effectiveness of an inhaled oxytocin product (IHO) in Bangladesh and Ethiopia. Methods A decision analytic model was developed to assess the cost-effectiveness of IHO for the prevention of PPH compared to the standard of care in Bangladesh and Ethiopia. In Bangladesh, introduction of IHO was modelled in all public facilities and home deliveries with or without a skilled attendant. In Ethiopia, IHO was modelled in all public facilities and home deliveries with health extension workers. Costs (costs of introduction, PPH prevention and PPH treatment) and effects (PPH cases averted, deaths averted) were modelled over a 12-month program. Life years gained were modelled over a lifetime horizon (discounted at 3%). Cost of maintaining the cold chain or effects of compromised oxytocin quality (in the absence of a cold chain) were not modelled. Results In Bangladesh, IHO was estimated to avert 18,644 cases of PPH, 76 maternal deaths and 1954 maternal life years lost. This also yielded a cost-saving, with the majority of gains occurring among home deliveries where IHO would replace misoprostol. In Ethiopia, IHO averted 3111 PPH cases, 30 maternal deaths and 767 maternal life years lost. The full IHO introduction program bears an incremental cost-effectiveness ratio (ICER) of between 2 and 3 times the per-capita Gross Domestic Product (GDP) ($1880 USD per maternal life year lost) and thus is unlikely to be considered cost-effective in Ethiopia. However, the ICER of routine IHO administration considering recurring cost alone falls under 25% of per-capita GDP ($175 USD per maternal life-year saved). Conclusions IHO has the potential to expand access to uterotonics and reduce PPH-associated morbidity and mortality in high burden settings. This can facilitate reduced spending on PPH management, making the product highly cost-effective in settings where coverage of institutional delivery is lagging.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::37be73b6fadb29e34e4ebe23b8770a75Test
http://link.springer.com/article/10.1186/s12916-020-01658-yTest

المؤلفون: Abebaw Minaye, Michelle P. McIntosh, Pete Lambert, Alula M. Teklu, Victoria L. Oliver, Moti Tolera

المصدر: Research in Social and Administrative Pharmacy. 16:535-543

مصطلحات موضوعية: Biomedical Research, Health Personnel, Supply chain, Pharmaceutical Science, Pharmacy, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Health care, Humans, 030212 general & internal medicine, Qualitative Research, Government, 030219 obstetrics & reproductive medicine, business.industry, Postpartum Hemorrhage, Focus Groups, Public relations, Focus group, Enabling, New product development, Female, Ethiopia, Business, Implementation research, Qualitative research

الوصف: Background The launch of novel pharmaceuticals in the developing world faces significant barriers that can delay or ultimately inhibit uptake. Implementation research can provide an understanding of factors influencing the introduction and scale up of a new product and thus can inform implementation strategy development. Objective This study explored the factors likely to influence introduction of a novel oxytocin formulation for the prevention of postpartum hemorrhage in Ethiopia. Methods Qualitative research methods were used to assess barriers and enablers associated with pre-determined domains: regulatory approval, pricing, supply and demand side advocacy, policy inclusion, end-user training and drug supply. Data were collected through focus group discussions and in-depth interviews with community members, healthcare providers and key informants. Verbatim transcripts were translated to English and analyzed using a thematic content framework. Results Approval from stringent regulatory bodies was an enabler for gaining national regulatory approval. Purchasers (government and patients) expressed price sensitivity but would be willing to pay a price comparable to or higher than current alternatives if improved quality is delivered. Endorsement from the World Health Organization was described as critical for national policy inclusion. Supply side advocacy should be directed towards the Ministry of Health, which is receptive to advice from reputable agencies with whom they have an existing relationship. Demand side advocacy should be delivered through existing health system channels such as Ministry of Health authorities (for healthcare workers) and community health workers (for community members). The requirement to purchase the product directly from a single manufacturer was highlighted as a potential barrier for entry into the local supply chain. Conclusion This study highlighted several barriers and enablers associated with the introduction of a new drug product into the health system of Ethiopia. An advanced understanding of these influences can inform the design of locally-appropriate implementation strategies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::91680043c6ef9d4fc5f54bab35b5f174Test
https://doi.org/10.1016/j.sapharm.2019.07.011Test

المؤلفون: Michael R. Whittaker, Ben J. Boyd, Colin W. Pouton, Lisa M. Kaminskas, Michelle P. McIntosh, Shadabul Haque

المصدر: Current Nanoscience

مصطلحات موضوعية: ethyl acetate, Materials science, Dispersity, Biomedical Engineering, Pharmaceutical Science, Medicine (miscellaneous), Nanoparticle, Bioengineering, 02 engineering and technology, 030226 pharmacology & pharmacy, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Dynamic light scattering, chemistry.chemical_classification, emulsion, Aqueous solution, technology, industry, and agriculture, solvent diffusion, PLGA, Polymer, 021001 nanoscience & nanotechnology, Solvent, chemistry, Chemical engineering, drug delivery, nanoparticles, Particle size, 0210 nano-technology, Biotechnology

الوصف: Background: Poly(d,l-lactide-co-glycolide) (PLGA) based biodegradable nanoparticles are of key interest for the development of controlled release drug delivery systems and for other biomedical applications. It has been reported that PLGA polymers can be converted into colloidal nanoparticulate systems by various techniques, such as emulsification-diffusion, emulsificationevaporation, interfacial deposition, salting out, dialysis and nanoprecipitation. Emulsificationevaporation with water immiscible solvents including dichloromethane and chloroform has been the preferred method for the synthesis of PLGA nanoparticles due to the low boiling point and limited water solubility of these solvents. We and others, however, have found that when water-immiscible solvents are used for the synthesis of PLGA nanoparticles, particle aggregation, non-uniform particle size and multimodal size distribution are commonly encountered problems. This suggests that the synthesis of PLGA nanoparticles using water immiscible solvents is highly sensitive to small procedural variations that affect overall reproducibility. Objective: This study presents a simple and robust procedure for the preparation of PLGA nanoparticles with very small batch to batch variability ( Results: The results showed that the emulsification solvent diffusion method teamed with partially water-miscible solvents, such as ethyl acetate, is a versatile approach for the preparation of PLGA nanoparticles with highly reproducible sizes (between 50 and 400 nm) and zeta potentials (between - 30 and +30 mV), with relatively narrow polydispersity. Conclusion: Emulsification-diffusion with ethyl acetate is, therefore, a more reliable alternative to several existing procedures for the reproducible and refined synthesis of PLGA nanoparticles.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d9e5420630470c3ddd9fb0fee638c065Test
http://europepmc.org/articles/PMC6225335Test

المؤلفون: Juliet Butler, Katherine S. Ong, Michelle P. McIntosh, Brian Lilley, Barbara Francis, Daniel Perkins, Tri-Hung Nguyen, Susan Cox

المصدر: European Journal of Drug Metabolism and Pharmacokinetics

مصطلحات موضوعية: Adult, Male, medicine.medical_specialty, Adolescent, Cmax, Placebo, 030226 pharmacology & pharmacy, digestive system, Mass Spectrometry, law.invention, Cohort Studies, 03 medical and health sciences, Food-Drug Interactions, Young Adult, 0302 clinical medicine, Randomized controlled trial, Pharmacokinetics, Double-Blind Method, law, Internal medicine, medicine, Cannabidiol, Humans, Pharmacology (medical), Original Research Article, Adverse effect, Pharmacology, Dose-Response Relationship, Drug, business.industry, Middle Aged, Lipids, digestive system diseases, surgical procedures, operative, Tolerability, 030220 oncology & carcinogenesis, Area Under Curve, Cohort, Anticonvulsants, Female, business, Cohort study, Chromatography, Liquid, Half-Life

الوصف: Background There is increasing interest in the use of purified cannabidiol (CBD) as a treatment for a wide range of conditions due to its reported anti-inflammatory, anxiolytic, antiemetic and anticonvulsant properties. Objective The objective of this study was to assess the safety, tolerability and pharmacokinetics of a single ascending dose of a new lipid-based oral formulation of CBD in healthy volunteers after a high-fat meal. Methods A total of 24 eligible healthy volunteers (aged 18–48 years) were randomised to one of three sequential cohorts (each with six active and two placebo subjects). Cohort 1 received 5 mg/kg CBD or placebo, cohort 2 received 10 mg/kg CBD or placebo (cohort 2), and cohort 3 received 20 mg/kg CBD or placebo. Data relating to adverse events, vital signs, clinical laboratory assessments, 12-lead ECGs, physical examinations and concomitant medications were collected to assess safety and tolerability. Blood samples were collected up to 8 days postdose and plasma was analysed by liquid chromatography and mass spectrometry to assess the pharmacokinetics of the CBD formulation. Results CBD was well tolerated in the healthy volunteers (mean age: 24.0 years) treated with a single oral dose of CBD. There were no safety concerns with increasing the dose and the safety profiles of the CBD-treated and placebo-treated subjects were similar. The most frequently reported treatment emergent adverse events (TEAEs) were headache (17%) and diarrhoea (8%). There were no reported serious adverse events (SAEs) and no clinical laboratory findings, vital signs, ECGs or physical examination findings that were reported as TEAEs or were of clinical significance during the study. After a high-fat meal, CBD was detected in plasma samples at 15 min postdose; the median time to maximum plasma concentration (Tmax) was 4 h across all three CBD dose cohorts. The CBD plasma exposure [maximum observed plasma concentration (Cmax) and the area under the concentration–time curve (AUC)] increased in a dose-proportional manner and declined to levels approaching the lower level of quantification by day 8. The terminal elimination half-life was approximately 70 h, suggesting that 2–3 weeks are needed to fully eliminate CBD. Conclusions This new CBD formulation demonstrated a favourable safety and tolerability profile in healthy volunteers that was consistent with the profiles reported for other purified CBD products. No severe or serious AEs were observed in this study and there were no safety concerns. Trial Registration ACTRN12618001424291. Registered August 2018.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d539c4505cba18b8217115a3e55af731Test
https://pubmed.ncbi.nlm.nih.gov/32409982Test

المؤلفون: Megan Rauscher, Rutendo Kuwana, Lawrence Evans, Peter Lambert, Fiona Theunissen, Michelle P. McIntosh, Mariana Widmer, Helen H. Petach, Beth Yeager

المصدر: Journal of Pharmaceutical Policy and Practice
Journal of Pharmaceutical Policy and Practice, Vol 13, Iss 1, Pp 1-13 (2020)

مصطلحات موضوعية: Supply chain, media_common.quotation_subject, lcsh:RS1-441, Pharmacy, Review, Safeguarding, lcsh:Pharmacy and materia medica, 03 medical and health sciences, 0302 clinical medicine, Procurement, medicine, Operations management, Quality (business), 030212 general & internal medicine, Cold chain, media_common, 030219 obstetrics & reproductive medicine, business.industry, Health Policy, lcsh:RM1-950, medicine.disease, Harm, lcsh:Therapeutics. Pharmacology, Maternal death, business

الوصف: Background The use of quality injectable oxytocin effectively prevents and treats postpartum hemorrhage, the leading cause of maternal death worldwide. In low- and middle-income countries (LMICs), characteristics of oxytocin—specifically its heat sensitivity—challenge efforts to ensure its quality throughout the health supply chain. In 2019, WHO, UNFPA and UNICEF released a joint-statement to clarify and recommend that oxytocin should be kept in the cold chain (between 2 and 8 °C) during transportation and storage; however, confusion among stakeholders in LMICs persists. Objectives and methods To further support recommendations in the WHO/UNFPA/UNICEF joint-statement, this paper reviews results of oxytocin quality testing in LMICs, evaluates product stability considerations for its management and considers quality risks for oxytocin injection throughout the health supply chain. This paper concludes with a set of recommended actions to address the challenges in maintaining quality for a heat sensitive pharmaceutical product. Results Due to the heat sensitivity of oxytocin, its quality may be degraded at numerous points along the health supply chain including: At the point of manufacture, due to poor quality active pharmaceutical ingredients; lack of sterile manufacturing environments; or low-quality manufacturing processes During storage and distribution, due to lack of temperature control in the supply chain, including cold chain at the end user health facility Safeguarding the quality of oxytocin falls under the purview of national medicines regulatory authorities; however, regulators in LMICs may not adhere to good regulatory practices. Conclusions Storing oxytocin from 2 to 8 °C throughout the supply chain is important for maintaining its quality. While short temperature excursions may not harm product quality, the cumulative heat exposure is generally not tracked and leads to degradation. National and sub-national policies must prioritize procurement of quality oxytocin and require its appropriate storage and management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f3ae2cd86619e08a170729a8ac14e1cTest
http://europepmc.org/articles/PMC7227300Test

المؤلفون: Michelle P. McIntosh, Marcy Powell, Disala Fernando, Susan Fowles, Sunita Singh, Ashutosh Gupta, Ian Schneider, Sarah Siederer, Peter Lambert, Duncan Richards

المصدر: EBioMedicine, Vol 22, Iss C, Pp 249-255 (2017)
EBioMedicine

مصطلحات موضوعية: Spirometry, Adult, Inhaled oxytocin, lcsh:Medicine, Phase 1, Placebo, Oxytocin, Injections, Intramuscular, General Biochemistry, Genetics and Molecular Biology, Drug Administration Schedule, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Pharmacokinetics, Administration, Inhalation, medicine, Humans, 030212 general & internal medicine, Dosing, Adverse effect, lcsh:R5-920, 030219 obstetrics & reproductive medicine, medicine.diagnostic_test, Inhalation, business.industry, lcsh:R, General Medicine, Healthy Volunteers, Postpartum hemorrhage, Tolerability, Premenopause, Anesthesia, Area Under Curve, Female, business, lcsh:Medicine (General), hormones, hormone substitutes, and hormone antagonists, medicine.drug, Research Paper

الوصف: Background The utility of intramuscular (IM) oxytocin for the prevention of postpartum hemorrhage in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. We evaluated the safety, tolerability and pharmacokinetics (PK) of a heat-stable, inhaled (IH) oxytocin formulation. Methods This phase 1, randomized, single-center, single-blind, dose-escalation, fixed-sequence study (NCT02542813) was conducted in healthy, premenopausal, non-pregnant, non-lactating women aged 18–45 years. Subjects initially received IM oxytocin 10 international units (IU) on day 1, IH placebo on day 2, and IH oxytocin 50 μg on day 3. Subjects were then randomized 4:1 using validated GSK internal software to IH placebo or ascending doses of IH oxytocin (200, 400, 600 μg). PK was assessed by comparing systemic exposure (maximum observed plasma concentration, area under the concentration-time curve, and plasma concentrations at 10 and 30 min post dose) for IH versus IM oxytocin. Adverse events (AEs), spirometry, laboratory tests, vital signs, electrocardiograms, physical examinations, and cardiac telemetry were assessed. Findings Subjects were recruited between September 14, 2015 and October 12, 2015. Of the 16 subjects randomized following initial dosing, 15 (IH placebo n = 3; IH oxytocin n = 12) completed the study. IH (all doses) and IM oxytocin PK profiles were comparable in shape. However, systemic exposure with IH oxytocin 400 μg most closely matched IM oxytocin 10 IU. Systemic exposure was approximately dose proportional for IH oxytocin. No serious AEs were reported. No clinically significant findings were observed for any safety parameters. Interpretation These data suggest that similar oxytocin systemic exposure can be achieved with IM and IH administration routes, and no safety concerns were identified with either route. The inhalation route may offer the opportunity to increase access to oxytocin for women giving birth in resource-poor settings.
Highlights • First-in-human study of a heat-stable, dry powder oxytocin formulation for oral inhalation using a simple inhaler device • Data suggest that similar oxytocin systemic exposure can be achieved with intramuscular and inhaled administration routes. • This could provide an effective delivery system for prevention of postpartum hemorrhage in women in resource-poor settings. Intramuscular or intravenous oxytocin is the gold standard preventative therapy for postpartum hemorrhage (PPH). However, the utility of intramuscular oxytocin in resource-poor settings is limited by the requirement for temperature-controlled storage and skilled staff to administer the injection. The Innovation Countdown 2030 Initiative has estimated that the introduction of alternative, heat-stable formulations of oxytocin could prevent 146,000 maternal deaths over a period of 8 years. This study provides encouraging preliminary evidence that inhaled oxytocin can be delivered using a heat-stable dried powder for inhalation with no safety concerns. Establishing the clinical utility of this potential medicine will require further studies.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3c984a66a7a3f87778c1f5ca3bd8be3fTest
https://doi.org/10.1016/j.ebiom.2017.07.020Test

المؤلفون: Peter Lambert, Claire Louise McEvoy, Michelle P. McIntosh, Philip Wright, Kim Deadman, Rajpreet Singh Minhas, Luc Mulimbalimba Masururu, Tri-Hung Nguyen

المصدر: Journal of Global Health

مصطلحات موضوعية: Quality Control, media_common.quotation_subject, Oxytocin, 03 medical and health sciences, 0302 clinical medicine, Pregnancy, Environmental health, Health care, Medicine, Humans, Quality (business), 030212 general & internal medicine, Cold chain, media_common, 030219 obstetrics & reproductive medicine, business.industry, Health Policy, Mortality rate, Postpartum Hemorrhage, Public Health, Environmental and Occupational Health, Articles, medicine.disease, Democratic Republic of the Congo, Female, Sample collection, Health Facilities, Rural area, business, medicine.drug

الوصف: Background Oxytocin injection is the first line therapy for the prevention and treatment of postpartum haemorrhage (PPH), the leading cause of maternal mortality. Currently access to high quality oxytocin in low and middle-income countries (LMICs) is compromised by variable manufacturing quality and the requirement for cold chain supply and storage to prevent product deterioration. Previous studies of oxytocin ampoules sampled from Africa, the region with highest maternal mortality rates, indicate that over half do not contain the specified amount of oxytocin. International efforts continue to further understand the issues relating to oxytocin quality in LMICs and this study is the first to assess oxytocin quality in the Democratic Republic of Congo (DRC), a country that bears one of the highest global rates of maternal mortality (693 maternal deaths per 100 000 live births). Importantly, the study methodology includes the use of investigative analytical techniques to understand the cause of quality deficiencies and inform remedial measures. Methods The study involved sampling of oxytocin injection ampoules from public and private health care facilities (n = 15) in urban and rural areas within five provinces of the DRC. Where available, each sample comprised 20 ampoules of oxytocin injection (10 IU/mL) with smaller numbers collected where supplies were limited. Sample collection used overt sampling and mystery shopper approaches, as appropriate. Analysis of ampoules for oxytocin content and known degradation products utilised validated HPLC and LCMS methods, respectively. Sterility testing was conducted in accordance with the United States Pharmacopeia monograph. Results Eighty percent of ampoules collected contained less than 90% of the specified content. Known degradation products of oxytocin were identified, indicating likely exposure to elevated temperatures post-manufacture. All samples contained an unknown impurity at a level of approximately 12.3% (8.0-20.5%) of the oxytocin main band peak. No samples failed sterility testing. Conclusions There is evidence of a high prevalence of poor quality oxytocin ampoules in health facilities in the DRC likely resulting from both manufacturing quality issues and uncontrolled storage. A more comprehensive post-marketing surveillance study of oxytocin quality is warranted.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c59f6bb9f587e7dc8240aa1d7e419345Test
http://europepmc.org/articles/PMC6126516Test

المؤلفون: Richard John Prankerd, Robert T. Forbes, Tomas Sou, Lisa M. Kaminskas, Michelle P. McIntosh, David Av Morton, Jason Gray

المصدر: Powder Technology. 287:248-255

مصطلحات موضوعية: chemistry.chemical_classification, Chemistry, General Chemical Engineering, Disaccharide, Excipient, 02 engineering and technology, Polymer, 021001 nanoscience & nanotechnology, 030226 pharmacology & pharmacy, Trehalose, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Polyol, Chemical engineering, Spray drying, Sodium citrate, medicine, Organic chemistry, Mannitol, 0210 nano-technology, medicine.drug

الوصف: For a dry powder formulation platform to be suitable for pulmonary delivery of potent biopharmaceuticals, e.g., proteins and peptides, it has to be not only efficiently and reproducibly aerosolisable, but also capable of creating a matrix suitable for stabilising the relevant biomacromolecules at temperatures appropriate for storage and distribution. This study systematically evaluated the use of excipient compounds covering a range of molecular sizes: i.e., from polyol (mannitol) and disaccharide (trehalose), to polysaccharide (inulin) and synthetic polymer (PVP K30), in conjunction with other small molecule excipients. It is recognised that larger molecular weight excipients with higher Tg values are less prone to recrystallisation, however there is limited data around the potential for the inclusion of these compounds in inhalable dry powder delivery systems, where historically the focus has been on employing mono- or disaccharides. The results demonstrated that the polymer/leucine systems retained an appropriately high Tg in spite of the relatively high moisture content after spray-drying. The results also showed that sodium citrate, in contrast to glycine and leucine, was effective in inhibiting crystallisation of spray-dried mannitol. The findings demonstrated the synergistic benefits achieved from the concurrent use of several excipients on spray-dried mannitol which have not been previously reported: leucine as a particle formation agent, sodium citrate as a glass-forming agent, and glycine as a morphological modifier.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::2ccf71de22f7bf77404db69a2e19fe87Test
https://doi.org/10.1016/j.powtec.2015.10.008Test

المؤلفون: Richard John Prankerd, Philip Wright, Tri-Hung Nguyen, Seloi Mogatle, Rajpreet Singh Minhas, Peter Lambert, Kim Deadman, Claire Louise McEvoy, Michelle P. McIntosh

المصدر: BMJ Open

مصطلحات موضوعية: Drug Storage, Population, Observational assessment, Temperature cycling, Oxytocin, Global Health, Ampoule, 03 medical and health sciences, 0302 clinical medicine, Drug Stability, Medicine, 030212 general & internal medicine, Food science, education, Drug Packaging, maternal medicine, education.field_of_study, 030219 obstetrics & reproductive medicine, business.industry, Research, Temperature, General Medicine, stability, Postpartum haemorrhage, Relative stability, injection, postpartum haemorrhage, Oxytocin Injection, business, medicine.drug

الوصف: IntroductionOxytocin, administered via injection, is recommended by WHO for the prevention and treatment of postpartum haemorrhage. However, the susceptibility of oxytocin injection to thermal degradation has led WHO and UNICEF to recommend cold-chain storage of all oxytocin products. Nevertheless, some oxytocin products supplied to the global market are labelled for storage at ≤25°C, often with a shorter shelf-life relative to products labelled for refrigeration. Differences in labelled storage requirements can lead to uncertainties among stakeholders around the relative stability of oxytocin products and specifically whether ≤25°C products are more resistant to degradation. Such confusion can potentially influence policies associated with procurement, distribution, storage and the use of oxytocin in resource-poor settings.ObjectivesTo compare the stability of oxytocin injection ampoules formulated for storage at ≤25°C with those labelled for refrigerated storage.DesignAccelerated and temperature cycling stability studies were performed with oxytocin ampoules procured by the United Nations Population Fund (UNFPA) from four manufacturers.MethodUsing oxytocin ampoules procured by UNFPA, accelerated stability (up to 120 days) and temperature cycling (up to 135 days between elevated and refrigerated temperatures) studies were performed at 30°C, 40°C and 50°C. Oxytocin content was quantified using a validated HPLC-UV method.ResultsAll ampoules evaluated exhibited similar stability profiles under accelerated degradation conditions with the exception of one product formulated for ≤25°C storage, where the rate of degradation increased at 50°C relative to other formulations. Similar degradation trends at elevated temperatures were observed during temperature cycling, while no significant degradation was observed during refrigerated periods of the study.ConclusionOxytocin ampoules formulated for non-refrigerated storage demonstrated comparable stability to those labelled for refrigerated storage and should not be interpreted by stakeholders as offering a more stable alternative. Furthermore, these products should not be procured for use in territories with high ambient temperatures, where all oxytocin injection products should be supplied and stored under refrigerated conditions.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::82392fd5466254d6f5591d2f2b64dc34Test
https://doi.org/10.1136/bmjopen-2019-029083Test

المؤلفون: Pete Lambert, Kyu Kyu Than, Yasmin Mohamed, Stanley Luchters, Victoria L. Oliver, Michelle P. McIntosh, Thazin La

المصدر: BMJ OPEN
BMJ Open

مصطلحات موضوعية: Adult, auxiliary midwives, Mothers, Cold storage, Myanmar, Midwifery, Oxytocin, Health Services Accessibility, Interviews as Topic, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Nursing, Pregnancy, Intervention (counseling), Administration, Inhalation, Health care, Medicine and Health Sciences, Humans, Medicine, Community Health Services, 030212 general & internal medicine, Product (category theory), Community-based care, Qualitative Research, Home Childbirth, community-based care, 030219 obstetrics & reproductive medicine, inhaled oxytocin, business.industry, Research, Postpartum Hemorrhage, Usability, General Medicine, Focus Groups, Patient Acceptance of Health Care, Delivery, Obstetric, task-shifting, Focus group, COVERAGE, postpartum haemorrhage, Feasibility Studies, Female, Public Health, Thematic analysis, business

الوصف: ObjectiveThis study assessed the potential operational feasibility and acceptability of a heat-stable, inhaled oxytocin (IOT) product for community-based prevention of postpartum haemorrhage in Myanmar.MethodsA qualitative inquiry was conducted between June 2015 and February 2016 through focus group discussions and in-depth interviews. Research was conducted in South Dagon township (urban setting) and in Ngape and Thanlyin townships (rural settings) in Myanmar. Eleven focus group discussions and 16 in-depth interviews were conducted with mothers, healthcare providers and other key informants. All audio recordings were transcribed verbatim in Myanmar language and were translated into English. Thematic content analysis was done using NVivo software.ResultsFuture introduction of an IOT product for community-based services was found to be acceptable among mothers and healthcare providers and would be feasible for use by lower cadres of healthcare providers, even in remote settings. Responses from healthcare providers and community members highlighted that midwives and volunteer auxiliary midwives would be key advocates for promoting community acceptance of the product. Healthcare providers perceived the ease of use and lack of dependence on cold storage as the main enablers for IOT compared with the current gold standard oxytocin injection. A single-use disposable device with clear pictorial instructions and a price that would be affordable by the poorest communities was suggested. Appropriate training was also said to be essential for the future induction of the product into community settings.ConclusionIn Myanmar, where home births are common, access to cold storage and skilled personnel who are able to deliver injectable oxytocin is limited. Among community members and healthcare providers, IOT was perceived to be an acceptable and feasible intervention for use by lower cadres of healthcare workers, and thus may be an alternative solution for the prevention of postpartum haemorrhage in community-based settings in the future.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e06aa63859337d8668f7600027c878daTest
https://doi.org/10.1136/bmjopen-2018-022140Test