Potentially harmful excipients in neonatal medicines: a pan-European observational study

2015 ◽  
Vol 100 (7) ◽  
pp. 694-699 ◽  
Author(s):  
Georgi Nellis ◽  
Tuuli Metsvaht ◽  
Heili Varendi ◽  
Karolin Toompere ◽  
Jana Lass ◽  
...  
Keyword(s):  
Propylene Glycol ◽  
Anatomical Therapeutic Chemical ◽  
Demographic Data ◽  
Active Pharmaceutical Ingredient ◽  
Geographical Region ◽  
Polysorbate 80 ◽  
Free Products ◽  
Saccharin Sodium ◽  
Anatomical Therapeutic Chemical Class ◽  
Harmful Excipients

ObjectivesWe aimed to describe administration of eight potentially harmful excipients of interest (EOI)—parabens, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol and benzalkonium chloride—to hospitalised neonates in Europe and to identify risk factors for exposure.MethodsAll medicines administered to neonates during 1 day with individual prescription and demographic data were registered in a web-based point prevalence study. Excipients were identified from the Summaries of Product Characteristics. Determinants of EOI administration (geographical region, gestational age (GA), active pharmaceutical ingredient, unit level and hospital teaching status) were identified using multivariable logistical regression analysis.ResultsOverall 89 neonatal units from 21 countries participated. Altogether 2095 prescriptions for 530 products administered to 726 neonates were recorded. EOI were found in 638 (31%) prescriptions and were administered to 456 (63%) neonates through a relatively small number of products (n=142; 27%). Parabens, found in 71 (13%) products administered to 313 (43%) neonates, were used most frequently. EOI administration varied by geographical region, GA and route of administration. Geographical region remained a significant determinant of the use of parabens, polysorbate 80, propylene glycol and saccharin sodium after adjustment for the potential covariates including anatomical therapeutic chemical class of the active ingredient.ConclusionsEuropean neonates receive a number of potentially harmful pharmaceutical excipients. Regional differences in EOI administration suggest that EOI-free products are available and provide the potential for substitution to avoid side effects of some excipients.

scholarly journals Potentially harmful excipients in neonatal medications: a multicenter nationwide observational study in Japan

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Jumpei Saito ◽  
Naomi Nadatani ◽  
Makoto Setoguchi ◽  
Masahiko Nakao ◽  
Hitomi Kimura ◽  
...  
Keyword(s):  
Observational Study ◽  
Benzyl Alcohol ◽  
Propylene Glycol ◽  
Demographic Data ◽  
Daily Intake ◽  
Package Insert ◽  
Prescription Data ◽  
Polysorbate 80 ◽  
Nationwide Observational Study ◽  
Harmful Excipients

Abstract Background A multicenter investigation of neonate exposure to potentially harmful excipients (PHEs) in neonatal intensive care units (NICUs) in Japan has not been conducted. Methods A multicenter nationwide observational study was conducted. Neonate patient demographic data and information on all medicines prescribed and administered during hospitalization on 1 day between November 2019 and March 2021 were extracted from the medical records. Nine PHEs, paraben, polysorbate 80, propylene glycol, benzoates, saccharin sodium, sorbitol, ethanol, benzalkonium chloride, and aspartame, were selected. PHEs were identified from the package insert and the Interview Form. The quantitative daily exposure was calculated if quantitative data were available for each product containing the PHE. Results Prescription data was collected from 22 NICUs in Japan. In total, 343 neonates received 2360 prescriptions for 426 products containing 228 active pharmaceutical ingredients. PHEs were found in 52 (12.2%) products in 646 (27.4%) prescriptions for 282 (82.2%) neonates. Benzyl alcohol, sodium benzoates, and parabens were the most common PHEs in parenteral, enteral, and topical formulations, respectively. Quantitative analysis showed that 10 (10%), 38 (42.2%), 37 (94.9%), and 9 (39.1%) neonates received doses exceeding the acceptable daily intake of benzyl alcohol, polysorbate 80, propylene glycol, and sorbitol, respectively. However, due to the lack of quantitative information for all enteral and topical products, accurate daily PHE exposure could not be quantified. Conclusions Neonates admitted to NICUs in Japan were exposed to PHEs, and several of the most commonly prescribed medicines in daily clinical practice in NICUs contained PHEs. Neonate PHE exposure could be reduced by replacing these medicines with available PHE-free alternatives.

scholarly journals P47 Extent of paediatric exposure to pharmaceutical excipients: an exploratory study

2020 ◽  
Vol 105 (9) ◽  
pp. e31.1-e31
Author(s):  
Mohammed AbouDaya ◽  
Stephen Tomlin ◽  
Asia N Rashed
Keyword(s):  
Propylene Glycol ◽  
Dosage Forms ◽  
List Type ◽  
Liquid Formulation ◽  
Solid Dosage Forms ◽  
Patient Factors ◽  
Solid Dosage ◽  
Oral Liquid ◽  
Harmful Excipients

AimThe assumption that excipients are inactive therefore non-harmful to patients is a declining opinion due to raised safety concerns of excipient activity, particularly in children.1 There is limited data on the safety of excipients in children and a lack of standardisation of the risk-benefit use of excipients in the different paediatric populations.2 This study aimed to investigate the extent of excipient exposure in children taking long-term oral liquids, admitted to Hospital, and to identify whether patients could be switched to a solid alternative due to the harm posed from liquid formulations.MethodA prospective observational study conducted in a UK paediatric hospital. The electronic medication chart for hospitalised children aged 0–18 years on long-term (for ≥6 weeks) oral liquid medicines, were reviewed over a four-week period. A priority list of eight excipients (called harmful excipients) with known reported hazards was developed based on literature: propylene glycol, ethanol, parabens, benzyl alcohol, aspartame, sorbitol, polysorbate 80 and benzoic acid. The list was used to determine the extent of children exposure to the harmful excipients. Considering patient factors (age, swallowing ability, treated condition), prescribed dose and availability of solid dosage forms, the included long-term liquid medicines were assessed for a potential solid form alternative by a specialist paediatric clinical pharmacist.ResultsA total of 302 oral liquid medicine formulations prescribed for 60 patients (age range 10 days – 17 years) were included in the study, of which 68.9% (208/302) were long-term oral liquid formulations. The 208 oral liquid formulation contained a total of 1044 excipients resulted in 17.4 (± 9) excipients per patients. Majority of patients (98.3%, 59/60) were exposed to at least one harmful excipient in their medicines. Children aged 2–11 years and 6–11 years were exposed the most to harmful excipients (mean 8.2 ± 4.9 exposure per patient). Parabens (81.7%, 49/60) was the most common harmful excipient patients were exposed to, followed by sorbitol (76.7%, 46/60), ethanol (75.0%, 45/60) and propylene glycol (70.0%, 42/60). Considering patient factors, prescribed dose and availability of solid formulations, it was found that almost third of the prescribed long-term oral liquid medicines (33.0%, 68/208) could be switched to tablet or capsule forms by pharmacist without any change to the prescribed dose. While for another 3.4% (7/208) long-term liquid medicines could be switched to solid dosage forms with prescriber approval, as prescribed doses would need to be adjusted slightly.ConclusionThe study highlights the extent of excipients exposure in children on long-term oral liquid medicines, many of which could potentially be harmful. Healthcare professionals should aim to reduce the long-term risks of excipients by providing an oral solid substitute to replace oral liquid formulation, where possible, and ensuring excipients are within safe, acceptable limits.ReferencesFabiano V, Mameli C, Zuccotti GV. Paediatric pharmacology: remember the excipients. Pharmacol Res 2011;63:362–365.Buckley L, Salunke S, Thompson K, et al. Challenges and strategies to facilitate formulation development of pediatric drug products: Safety qualification of excipients. Int J Pharm 2018; 536:563–569.

scholarly journals DEVELOPMENT OF LIQUISOLID FORMULATION FOR IMPROVED SUSTAINED RELEASE OF PROPRANOLOL HYDROCHLORIDE

2021 ◽  
pp. 210-216
Author(s):  
ALIYAH ALIYAH ◽  
EMILIA UTOMO ◽  
ANDI DIAN PERMANA ◽  
ERNAWATI
Keyword(s):  
Drug Release ◽  
Sustained Release ◽  
Propylene Glycol ◽  
Gastric Fluid ◽  
Angle Of Repose ◽  
Simulated Gastric Fluid ◽  
Polysorbate 80 ◽  
Propranolol Hydrochloride ◽  
Coating Materials ◽  
Simulated Intestinal Fluid

Objective: The aim of this study was to develop a liquisolid formulation of propranolol hydrochloride to obtain an improved sustained release profile by varying the ratio of liquid vehicles. Methods: In this study, propranolol hydrochloride (PPH) was dispersed in the combination of propylene glycol and polysorbate 80, as the liquid vehicles, with different ratios. Eudragit® RL and Aerosil® were used as carrier and coating materials, respectively, to produce a dry and free-flowing powder. In addition, HPMC was used to amplify the retardation effect. The prepared formulations were evaluated for its physicochemical properties, including loss on drying, flow rate, angle of repose calculation, drug content analysis, FT-IR spectroscopy, as well as dissolution studies. The obtained dissolution profiles were subsequently fitted to the mathematical model in order to determine the drug kinetics. Results: The results show that all formulations performed dry and free-flowing granules containing PPH in the range of 7-9%. Furthermore, all the prepared formulations were able to sustain the drug release for a total of 8 h in two different dissolution media, namely simulated gastric fluid and simulated intestinal fluid. F4 containing propylene glycol and polysorbate 80 (1:2) possessed the lowest drug release rate. It was also obtained that F1 and F3 followed first-order kinetics while F2, F4, and F5 complied with the Higuchi model. Conclusion: Overall, there was no difference in all the dissolution profiles based on the calculation of the difference and similarities factor.

Turning waste medicines to cost savings: A pilot study on the feasibility of medication recycling as a solution to drug wastage

2016 ◽  
Vol 31 (1) ◽  
pp. 35-41 ◽  
Author(s):  
Ming Ren Toh ◽  
Lita Chew
Keyword(s):  
Public Hospital ◽  
Hospice Care ◽  
Anatomical Therapeutic Chemical ◽  
Cost Savings ◽  
Potential Cost ◽  
Medical Clinics ◽  
Drug Classes ◽  
Medication Wastage ◽  
Anatomical Therapeutic Chemical Class ◽  
Chemical Class

Background: Unused medicines represent a major source of wastage in healthcare systems around the world. Previous studies have suggested the potential cost savings from recycling the waste medicines. However, issues of product safety and integrity often deter healthcare institutions from recycling donated medications. Aim: To evaluate the feasibility of medication recycling and to assess the actual cost savings from recycling waste medicines and whether reusability of waste medicines differed among various drug classes and donor sources. Design and setting: Donated medications from hospitals, private medical clinics and patients were collected and assessed using a medication recycling protocol in a hospice care setting from November 2013 through January 2014. Costs were calculated using a reference pricing list from a public hospital. Results: A total of 244 donations, amounting to 20,759 dosage units, were collected during the study period. Most donations (90.8%) were reusable, providing a total of S$5266 in cost savings. Less than 2 h daily was spent by a single pharmacy technician on the sorting and distributing processes. Medications donated by health facilities were thrice more likely to be reusable than those by patients (odds ratio = 3.614, 95% confidence interval = 3.127, 4.176). Medications belonging to Anatomical Therapeutic Chemical class G (0.0%), H (8.2%) and L (30.0%) were the least reusable. Conclusion: Most donated medications were reusable. The current protocol can be further streamlined to focus on the more reusable donor sources and drug classes and validated in other settings. Overall, we opine that it is feasible to practise medication recycling on a larger scale to reduce medication wastage.

scholarly journals Clinico-mycological study of onychomycosis

2019 ◽  
Vol 6 (1) ◽  
pp. 89
Author(s):  
Sumedha Ballal ◽  
Ishwara Bhat P. ◽  
Anil Abraham ◽  
Jayanthi Savio
Keyword(s):  
Clinical Features ◽  
Potassium Hydroxide ◽  
Standard Procedure ◽  
Demographic Data ◽  
Fungal Isolate ◽  
Geographical Region ◽  
Fungal Culture ◽  
Clinical Pattern ◽  
Clinical Type ◽  
Nail Involvement

<p class="abstract"><strong>Background:</strong> Onychomycosis is the most common infective nail disorder accounting for 30% of cutaneous mycoses. Though predominantly caused by dermatophytes, yeast and non-dermatophyte moulds have also been implicated. Aim of this study was to describe and analyse clinical and mycological pattern of onychomycosis.</p><p class="abstract"><strong>Methods:</strong> One hundred patients with onychomycosis diagnosed by direct potassium hydroxide microscopy and culture were included. Nail specimens were collected for fungal culture as per standard procedure. An analysis of demographic data, clinical features and mycological results was made.<strong></strong></p><p class="abstract"><strong>Results:</strong> Majority of the affected cases were between 19 to 85 years of age. Fingernail onychomycosis was seen in 41 patients, toenail was seen in 46 patients, concurrent involvement was seen in 13 patients. The predominant clinical pattern seen was distal lateral subungual type (70%). Culture was positive among 49% patients. Among these patients non dermatophyte growth was predominant (72%) showing. <em>Aspergillus </em>species (31%) and <em>Fusarium </em>species (31%), <em>Cladosporium</em> species (4%) and <em>Scytalidium </em>species (2%). <em>Trichophyton </em>species (16%) and <em>Candida </em>species<em> </em>(16%) were also isolated. The clinico-etiological correlation revealed that a single pathogen could give rise to more than one clinical type of onychomycosis. Non-Dermatophyte moulds were the most common isolate followed by yeasts and dermatophytes. This is in contrast to earlier studies from a similar geographical region where dermatophytes were the commonest pathogen.</p><p class="abstract"><strong>Conclusions:</strong> Non-dermatophyte moulds are emerging as the predominant isolate in onychomycosis. The clinical pattern of nail involvement showed no correlation with the fungal isolate.</p>

scholarly journals Excipients of inhaled medications with potential to cause adverse reactions

2021 ◽  
Vol 8 (3) ◽  
pp. 1109-1117
Author(s):  
Dejan Kusonić ◽  
Katarina Petronijević ◽  
Jelena Čanji-Panić ◽  
Nebojša Pavlović ◽  
Nemanja Todorović ◽  
...  
Keyword(s):  
Medical Devices ◽  
Benzalkonium Chloride ◽  
Adverse Reactions ◽  
Active Pharmaceutical Ingredient ◽  
Disodium Edta ◽  
International Regulations ◽  
Causative Agents ◽  
European Regulations ◽  
The Republic ◽  
Harmful Excipients

Introduction: In addition to the active pharmaceutical ingredient (API), the composition of the medicines also includes excipients which are only ideally completely pharmacologically inactive. It has been shown that excipients in inhaled preparations can cause effects opposite to the pharmacological effect of the medicine. Aim: The Aim of the study was to identify potentially harmful excipients in inhaled medicines approved in the Republic of Serbia. Material and Methods: The academic study was conducted during April 2021 and included the analysis of medicines that received a marketing authorization from the Medicines and Medical Devices Agency of Serbia (ALIMS). Qualitative compositions of inhaled medicines available in Summaries of product characteristics (SmPC) on the ALIMS's official website were observed. Excipients considered potentially harmful if they are recognised as excipients with known effect (EKE) in Serbian and European regulations. Results: Total of 46 inhalation preparations that are approved in Serbia were analyzed. In their composition were found 17 different excipients. By comparing appropriate domestic and European regulations three excipients from examined preparations that represent potential causative agents of adverse drug reactions (ADRs) were identified: lactose-monohydrate, ethanol and benzalkonium chloride. It has been shown that disodium EDTA is also a potential causative agent of ADRs, but it is not classified as EKE. Conclusion: Neither domestic nor international regulations have classified EDTA and its salts as EKE and they should be given special attention in the future as potential causative agents of ADRs. It has been shown that benzalkonium chloride is the only excipient that can lead to bronchospasm and it was found in two inhaled medicines.

scholarly journals Propylene Glycol Caprylate-Based Nanoemulsion Formulation of Plumbagin: Development and Characterization of Anticancer Activity

2022 ◽  
Vol 2022 ◽  
pp. 1-9
Author(s):  
Adrian Chrastina ◽  
John Welsh ◽  
Per Borgström ◽  
Veronique T. Baron
Keyword(s):  
Prostate Cancer ◽  
Particle Size ◽  
Cancer Cells ◽  
Propylene Glycol ◽  
Active Pharmaceutical Ingredient ◽  
Water Soluble ◽  
Hydrodynamic Diameter ◽  
Prostate Cancer Cells ◽  
Spontaneous Emulsification ◽  
Water Soluble Compound

Plumbagin, a bioactive naphthoquinone, has demonstrated potent antitumor potential. However, plumbagin is a sparingly water-soluble compound; therefore, clinical translation requires and will be facilitated by the development of a new pharmaceutical formulation. We have generated an oil-in-water nanoemulsion formulation of plumbagin using a low-energy spontaneous emulsification process with propylene glycol caprylate (Capryol 90) as an oil phase and Labrasol/Kolliphor RH40 as surfactant and cosurfactant excipients. Formulation studies using Capryol 90/Labrasol/Kolliphor RH40 components, based on pseudoternary diagram and analysis of particle size distribution and polydispersity determined by dynamic light scattering (DLS), identified an optimized composition of excipients for nanoparticle formulation. The nanoemulsion loaded with plumbagin as an active pharmaceutical ingredient had an average hydrodynamic diameter of 30.9 nm with narrow polydispersity. The nanoemulsion exhibited long-term stability, as well as good retention of particle size in simulated physiological environments. Furthermore, plumbagin-loaded nanoemulsion showed an augmented cytotoxicity against prostate cancer cells PTEN-P2 in comparison to free drug. In conclusion, we generated a formulation of plumbagin with high loading drug capacity, robust stability, and scalable production. Novel Capryol 90-based nanoemulsion formulation of plumbagin demonstrated antiproliferative activity against prostate cancer cells, warranting thus further pharmaceutical development.

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