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1.
Int J Pharm Compd ; 24(1): 14-19, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32023211

RESUMO

The U.S. Food and Drug Administration regulates outsourcing facilities with the same stringency they apply towards drug manufacturers. This means that outsourcing facilities, who must navigate the changing regulatory landscape to achieve and maintain 503B status, must now focus on qualifying container closure systems for their intended use. This article, the second in a two-part series, examines component selection and methods for demonstrating that the container closure system will protect and maintain the quality of the compounded drug and ensure that the compounded drug can be safely administered to a patient.


Assuntos
Embalagem de Medicamentos , Armazenamento de Medicamentos , Humanos , Estados Unidos , United States Food and Drug Administration
2.
Eur J Pharm Sci ; 141: 105102, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31655210

RESUMO

PURPOSE: To assess the physico-chemical stability of Voriconazole Eye-Drops (VED), when stored frozen and refrigerated once thawed, in 3 containers: Amber glass with a Low-Density PolyEthylene (LDPE) eyedropper, and two types of LDPE bottles: one classical and one with an innovative insert that maintains sterility after opening (Novelia® from Nemera). METHODS: Three batches of 1% VED (10 mL) were aseptically compounded from marketed injectable voriconazole (Vfend®) diluted in sterile water for injection. VEDs were stored for three months at -20 °C in amber glass (n = 32), classical LDPE (n = 32) or innovative LDPE (n = 31) bottles. Stability-indicating (HPLC-UV-DAD) and chiral chromatography methods were developed. The stability study was conducted according to GERPAC-SFPC guidelines. At each study time, the following parameters were controlled: visual aspect, voriconazole concentration, pH and osmolality. In addition, non-visible particle count, sterility and absence of racemisation (impurity D - (2S,3R)-voriconazole) were assessed at the beginning and end of the study. Results are expressed as mean ± standard deviation. Statistical analyses were performed using non-parametric tests (α < 5%) to compare containers. RESULTS: When stored frozen, concentration was between 95.2 ±â€¯1.4% and 103.6 ±â€¯1.3% of the initial concentration (C0) with no difference between the three containers (p = 0.564; non-significant). Fifteen days after thawing, concentration was between 97.1 ±â€¯1.6% and 98.6 ±â€¯0.8% of C0 with no difference between containers (p = 0.278 and 0.368 for VED thawed at room temperature and at 2-8 °C, respectively). pH remained stable between each time. Osmolality was slightly higher in glass (533.17 ±â€¯8.93 mOsm/Kg) than in plastic containers (522.17±3.31mOsm/Kg, classical LDPE; 517.5 ±â€¯12.42 mOsm/Kg, innovative LDPE) (p = 0.022). Sterility was preserved. Degradation product areas increased slightly but remained below the limit of quantification. Impurity D was never detected. CONCLUSION: We have demonstrated that the ability of the innovative container Novelia® to maintain VED physicochemical and microbiological stability does not differ from that of amber glass and classical LDPE containers. Real life studies are required to find out if there is a potential difference between Novelia® and other containers in terms of sterility preservation.


Assuntos
Antifúngicos/química , Soluções Oftálmicas/química , Voriconazol/química , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Congelamento , Vidro/química , Polietileno/química
3.
J Pharm Biomed Anal ; 177: 112839, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31505430

RESUMO

Parenteral amino acid solutions containing tryptophan tend to develop a yellow colouration upon storage. Hence, the aim of the present study was to find out whether tryptophan degradation products are the reason for the yellowing. The degree of discolouration and tryptophan degradation was examined by visual examination and UV/Vis measurements with respect to oxygen presence, pH value, and duration of steam sterilization. LC-UV analyses of autoclaved tryptophan solutions indicated eight degradation products, namely R,R/R,S 2-amino-3-(oxoindolin-3-yl)propanoic acid, R,R/R,S 2-amino-3-hydroxy-2-oxoindolin-3-yl)propanoic acids, cis/trans 3a-hydroxy-1,2,3,3a,8,8a-hexahydropyrrolo[2,3-b]indole-2-carboxylic acid, N´-formylkynurenine, and kynurenine. The proposed degradation products were confirmed by spiking of synthesized degradation products and LC-UV/MS analyses. The LC-UV analysis method was optimized and validated according to the ICH guideline Q2 (R1). Tryptophan stability in commercially available parenteral amino acid formulations was evaluated over a storing period of 12 months in two common types of primary packaging after autoclave procedure.


Assuntos
Cor , Soluções de Nutrição Parenteral/química , Controle de Qualidade , Espectrometria de Massas por Ionização por Electrospray/métodos , Triptofano/química , Cromatografia Líquida de Alta Pressão/métodos , Embalagem de Medicamentos/métodos , Embalagem de Medicamentos/normas , Estabilidade de Medicamentos , Armazenamento de Medicamentos/normas , Oxirredução , Soluções de Nutrição Parenteral/normas
4.
J Oncol Pharm Pract ; 26(1): 141-145, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31132937

RESUMO

INTRODUCTION: All guidelines necessitate wearing personal protective equipment during dispensing of oral anticancer drugs. This study aims to measure the degree of contamination on the press-through-package strips of oral anticancer drugs in Japan. METHOD: Surface contamination of the external packaging of anticancer drugs was examined by performing wipe tests at four hospitals and two community pharmacies. The following commercially available drugs were examined: Xeloda®, TS-1®, and methotrexate tablets and SA-1® and Rheumatrex® capsules. RESULTS: The wipe tests' results revealed that the contamination levels of Xeloda® and TS-1® tablets and SA-1® capsules were within their detection limits. In some facilities, the contamination levels on the press-through-package strips of Rheumatrex® capsules were 3.27 × 10-1, which is close to its detection limit. However, across all facilities, the contamination level of methotrexate tablets was above its detection limit. CONCLUSION: The results of this study suggested that adherence to oral anticancer drugs may not occur during manufacture or transportation. However, it may be due to the presence of pollutants in the facilities. Prevention of pollution in facilities might eliminate the need to wear personal protective equipment during dispensing of oral anticancer drugs.


Assuntos
Antineoplásicos/administração & dosagem , Contaminação de Medicamentos/prevenção & controle , Embalagem de Medicamentos/métodos , Contaminação de Equipamentos/prevenção & controle , Exposição Ocupacional/prevenção & controle , Antineoplásicos/análise , Embalagem de Medicamentos/normas , Monitoramento Ambiental/métodos , Monitoramento Ambiental/normas , Humanos , Japão/epidemiologia , Exposição Ocupacional/normas , Farmácias/normas
6.
Int J Pharm Compd ; 23(6): 454-461, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31751941

RESUMO

The U.S. Food and Drug Administration regulates outsourcing facilities with the same stringency they apply towards drug manufacturers. This means that outsourcing facilities, who must navigate the changing regulatory landscape to achieve and maintain 503B status, need to focus on qualifying container closure systems for their intended use. Container closure systems must be fit-for-purpose (i.e., suitable for in-use conditions relative to drug product stability over intended shelf-life and storage conditions). This article, the first of a two-part series, addresses the critical aspect of how to qualify systems for intended use regarding container closure integrity. The second part will address component selection.


Assuntos
Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Estados Unidos , United States Food and Drug Administration
9.
AAPS PharmSciTech ; 20(8): 313, 2019 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-31529232

RESUMO

An integrated approach based on QbD and PAT provides a systematic and innovative framework for product development, manufacturing, and quality risk management. In this context, the significance of the outcome of design of experiments (DOEs) to the selection of the product design, robust commercial manufacturing process, design space, and overall control strategy remains vital for the success of a drug product throughout its life cycle. This paper aims at discussing selected recent DOE case studies conducted during QbD-based and integrated QbD/PAT-based development of solid oral formulations and process improvement studies. The main focus of this paper is to highlight the rationales and importance of design selection during development and applications of mathematical models and statistical tools in analyzing DOE and PAT data for developing a design space, control strategy, and improved process monitoring. A total of 25 case studies (includes 9 PAT application studies) have been discussed in this paper which cover 11 manufacturing processes commonly utilized for solid dosage forms. Two case studies relevant to selection of packaging design for solid dosage forms are also briefly discussed to complete the scope. Overall, for a successful modern QbD approach, it is highly important that DOEs are conducted and analyzed in a logical sequence which involves designs that are phase-appropriate and quality-driven and facilitate both statistical and chemometric thinking at each development stage. This approach can result into higher regulatory flexibility along with lower economic burden during life cycle of a product, irrespective of regulatory path used (NDA or ANDA).


Assuntos
Formas de Dosagem , Desenho de Fármacos , Indústria Farmacêutica/normas , Embalagem de Medicamentos/normas , Controle de Qualidade , Composição de Medicamentos , Indústria Farmacêutica/métodos , Embalagem de Medicamentos/métodos , Humanos
10.
Nutrients ; 11(9)2019 Aug 23.
Artigo em Inglês | MEDLINE | ID: mdl-31450771

RESUMO

Emerging data suggest that intravenous ascorbic acid (AA) may be beneficial in patients with sepsis. Clinicians require data on stability of diluted AA for safe administration. We evaluated the stability of AA diluted in normal saline (NS) or 5% dextrose in water (D5W) solutions over 14 days at 25 °C and at 4 °C, protected from light, using concentrations of 37 mg/mL and 77 mg/mL (Sandoz) and 40 mg/mL and 92 mg/mL (Mylan). We also assessed stability of a 40 mg/mL solution (Mylan) at 25 °C exposed to light for 75 h. Concentrations were measured using liquid chromatographic separation with ultraviolet light detection on days 0, 0.33, 1, 1.33, 2, 3, 4, 7, 10 and 14. By day 14, solutions at 4 °C retained >97.72% of the initial concentration; at 25 °C, solutions retained >88.02% of the initial concentration, but visual changes were evident after day 2. Multiple linear regression demonstrated that study day and temperature (p < 0.001) but not solution type (p = 0.519), concentration (p = 0.677) or manufacturer (p = 0.808) were associated with the percentage remaining. At 75 h, degradation rates were similar in solutions protected from vs. exposed to light. In conclusion, AA solutions are stable for at least 14 days at 4 °C, with protection from light.


Assuntos
Ácido Ascórbico/química , Sepse/tratamento farmacológico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/efeitos da radiação , Composição de Medicamentos , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Glucose/química , Humanos , Infusões Intravenosas , Luz , Fotólise , Solução Salina/química , Sepse/diagnóstico , Temperatura , Fatores de Tempo
11.
Int J Pharm ; 567: 118493, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31279054

RESUMO

Effective inhaler therapy requires correct handling of the inhaler, including being able to prepare the inhaler for use. Motor function impairment and cognitive disabilities, may impose problems on patients with Parkinson's disease when they have to prepare medication, such as inhalers, for use. The aim of the present study was to examine whether Parkinson's patients are able to correctly prepare the Cyclops inhaler for use. At first, 12 patients, 6 in an off state and 6 in an on state, were asked to open 5 inhalers with ascending peel resistance of the cover foil. It was investigated up to which peel resistance they were able to successfully pull the foil from the inhaler. For the second part of the study, 48 participants, 24 on and 24 off, were asked to open 2 pouches and the 2 inhalers selected in part 1. For pouch 1, 70.8% of the patients in an on state and 58.3% in an off state were able to open the pouch correctly. For pouch 2, this was 79.2% and 75.0%, respectively. Both Cyclops inhalers were opened correctly by 95.8% of the participants in the on state and 91.7% of the participants in the off state.


Assuntos
Embalagem de Medicamentos , Inaladores de Pó Seco , Doença de Parkinson/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antiparkinsonianos/administração & dosagem , Feminino , Humanos , Levodopa/administração & dosagem , Masculino , Pessoa de Meia-Idade
12.
BMC Public Health ; 19(1): 971, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31331304

RESUMO

BACKGROUND: 'Yaa Chud' is a non-prescribed poly-pharmaceutical pack containing several types of drugs, including antibiotics and steroids, which can be purchased over the counter in Thailand for self-medication. Although it is illegal, it is still available at some community outlets. This study aimed to understand access to and use of Yaa Chud at the community level in order to raise awareness on its usage and to provide policy recommendations to address the problem. METHODS: This study employed qualitative methods, including in-depth interviews with 18 drug suppliers and 16 community members, and six focus group discussions. It included inventories from 17 drug suppliers. Data were collected in selected communities of the Kanchanaburi Demographic Surveillance System, located in the western region of Thailand.Thematic analysis was based upon the Health Services Utilization Model and conducted using the Open Code qualitative software program. RESULTS: Overcrowding, long waiting times, and a perceived unwelcoming environment at public health-care service outlets were identified as factors that drive people into the private sector, where loose regulation of drug laws facilitates access and use of Yaa Chud. Migrants and older people were most likely to seek and use Yaa Chud, especially for mild illness. Availability, easy access through a user's network, low cost, and perceived effectiveness were identified as factors that enable access and use of Yaa Chud. CONCLUSIONS: Though illegal in Thailand, Yaa Chud is likely to remain available for self-medication by community members, due to the persisting demand by the elderly and migrant workers. There is an urgent need to replace these mixed medications with better choices. Safer Yaa Chud may be a preferred, first-line health-care option, which could help reduce congestion in the formal health-care setting. At the same time, enforcement of regulatory compliance needs to be continued in order to stop the supply of unsafe Yaa Chud.


Assuntos
Embalagem de Medicamentos , Medicamentos sem Prescrição/provisão & distribução , Medicamentos sem Prescrição/uso terapêutico , Automedicação , Adulto , Idoso , Feminino , Grupos Focais , Humanos , Legislação de Medicamentos , Masculino , Pessoa de Meia-Idade , Tailândia , Adulto Jovem
13.
Int J Pharm ; 568: 118510, 2019 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-31302170

RESUMO

Pharmaceutical containers for parenterals have been predominantly manufactured using glass as a packaging material of choice, especially Type-I glass, since it has been regarded as a chemically inert and an effective container closure system (CCS). Nevertheless, there have been reports and recalls related to glass quality issues, such as breakage, flakes, and particles observed in marketed products. The novelty of this research is based on the knowledge gathered from our previously conducted risk assessments and establishing a comprehensive testing platform focused on risk factors for glass container failure modes and applicability to other types of pharmaceutical containers. The evaluation of container quality attributes was performed for three model glass vials using a mechanical and chemical durability testing platform: freeze-thaw, lyophilization, compression, scratch tests; visual inspection, pH, particle size analyses, extractable, leachable and imaging studies that were conducted under normal (4 and 25 °C), and stress condition (60 °C), respectively. The performance between the glass containers tested under certain stress conditions (failure modes) were variable and differentiated. The systematic platform testing approach shows the importance of lab-based risk evaluation in assessing common failure modes of pharmaceutical containers, since the quality attributes for injectable products are complex and can impact final product quality.


Assuntos
Embalagem de Medicamentos , Vidro , Liofilização , Teste de Materiais , Nutrição Parenteral , Controle de Qualidade
14.
Anesthesiology ; 131(2): 305-314, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31166244

RESUMO

BACKGROUND: Health care-associated hepatitis C virus outbreaks from contaminated medication vials continue to be reported even though most practitioners deny reusing needles or syringes. The hypothesis was that when caring for hepatitis C virus-infected patients, healthcare providers may inadvertently contaminate the medication vial diaphragm and that subsequent access with sterile needles and syringes can transfer hepatitis C virus into the medication, where it remains stable in sufficient quantities to infect subsequent patients. METHODS: A parallel-arm lab study (n = 9) was performed in which contamination of medication vials in healthcare settings was simulated using cell culture-derived hepatitis C virus. First, surface-contaminated vials were accessed with sterile needles and syringes, and then hepatitis C virus contamination was assessed in cell culture. Second, after contaminating several medications with hepatitis C virus, viral infectivity over time was assessed. Last, surface-contaminated vial diaphragms were disinfected with 70% isopropyl alcohol to determine whether disinfection of the vial surface was sufficient to eliminate hepatitis C virus infectivity. RESULTS: Contamination of medication vials with hepatitis C virus and subsequent access with sterile needles and syringes resulted in contamination of the vial contents in sufficient quantities to initiate an infection in cell culture. Hepatitis C virus remained viable for several days in several commonly used medications. Finally, a single or 2- to 3-s wipe of the vial diaphragm with 70% isopropyl alcohol was not sufficient to eliminate hepatitis C virus infectivity. CONCLUSIONS: Hepatitis C virus can be transferred into commonly used medications when using sterile single-use needles and syringes where it remains viable for several days. Furthermore, cleaning the vial diaphragm with 70% isopropyl alcohol is not sufficient to eliminate the risk of hepatitis C virus infectivity. This highlights the potential risks associated with sharing medications between patients.


Assuntos
Embalagem de Medicamentos , Contaminação de Equipamentos , Hepacivirus/crescimento & desenvolvimento , Agulhas/microbiologia , Seringas/microbiologia , Células Cultivadas
15.
Yakugaku Zasshi ; 139(9): 1185-1193, 2019 Sep 01.
Artigo em Japonês | MEDLINE | ID: mdl-31189749

RESUMO

The pramipexole extended-release (long acting) tablet, a D2 receptor agonist commonly used for the treatment of Parkinson's disease, has increasingly demonstrated usability for patients with long acting performance and patient adherence improvements. As a generic drug it is sold by six companies while a brand name drug is also marketed. As these formulations are hygroscopic it is described as such in package inserts so that tablets will only be removed from the press-through package (PTP) immediately before ingestion. It is often dispensed in one-dose packaging (ODP) as determined by a patient's physical functions and symptom characteristics. With ODP, quality control and ease of removal from the PTP are important factors. In this study we examined the stability of tablets in the ODP (25℃ RH75%) while also comparing the ease of handling of the seven products currently marketed in Japan. In the tablets' ODP, changes such as swelling and decreases in tablets hardness were observed in six formulations. Differences were found among the products in comparison of packaging material, required tablet extrusion strength, and ease of removal. Given the differences in PTP materials and hygroscopicity it is suggested that pharmacists must not only consider the drug formulations of products but also contribute to improvements in medication adherence for patients with poor hand-finger function.


Assuntos
Antiparkinsonianos , Agonistas de Dopamina , Embalagem de Medicamentos , Medicamentos Genéricos , Adesão à Medicação , Doença de Parkinson/tratamento farmacológico , Pramipexol , Preparações de Ação Retardada , Estabilidade de Medicamentos , Humanos , Japão , Receptores de Dopamina D2/agonistas , Inquéritos e Questionários , Comprimidos
16.
Int J Pharm ; 566: 513-519, 2019 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-31175992

RESUMO

The optical and swelling properties of gatifloxacin-loaded contact lens decrease owing to the precipitation of gatifloxacin (on hydration) in the matrix structure of the contact lens. This paper focuses on the use of Pluronic F68 both inside and outside (in the packaging solution) the contact lens to form micelles to dissolve the gatifloxacin precipitates and not limited to sustain the release of gatifloxacin. The aim of this study was to screen the critical variables affecting the optical and swelling properties of gatifloxacin-loaded contact lens. The independent variables investigated were the concentration of Pluronic F68 incorporated in the monomer solution to fabricate the lens (X1, %w/v), the concentration of Pluronic F68 in the packaging solution (X2, %w/v), the concentration of gatifloxacin incorporated in the monomer solution (X3, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during autoclave (X4, %w/v), the concentration of gatifloxacin incorporated in the packaging solution during extraction (X5, %w/v), the time (stabilization time) after the addition of gatifloxacin and Pluronic F68 to the monomer solution before the fabrication of the lens (X6, h), the pH of the packaging solution (X7), the temperature of the extracted solution (X8, °C), and the curing time for fabricating the contact lens (X9, min). The gatifloxacin-loaded contact lenses were characterized for their optical transmittances after sterilization on day 1 (Y1, %), optical transmittances after 7 days of sterilization (Y2, %) and swelling percentages after 7 days of sterilization (Y3, %). The selected variables showed responses that were in the ranges 53.5% to 97.2%, 51.3% to 92.6%, and 50.3% to 83.7% for Y1, Y2, and Y3, respectively. The data suggest that the presence of Pluronic F68 inside the contact lens (X1) reduced the optical and swelling properties of the contact lens, whereas the presence of Pluronic F68 in the packaging solution (X2) improved them through micelle formation. The other variables (X3 to X9) did not exhibit significant effects on the swelling and transmittance. This study revealed the potential of Plackett-Burman design to screen the selected critical variables that affected the optical and swelling properties of gatifloxacin-loaded contact lens.


Assuntos
Lentes de Contato , Gatifloxacina/química , Poloxâmero/química , Preparações de Ação Retardada/química , Desenho de Fármacos , Embalagem de Medicamentos , Micelas , Esterilização
17.
Talanta ; 201: 259-265, 2019 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-31122421

RESUMO

Medicines are meant to help people and treat their conditions and to promote general well-being of all members of the society. Unfortunately, this is being compromised by the distribution and sale of poor-quality medicines around the world, being a consequence of non-GMP manufacturing. In this study, the contamination of the outer primary packaging with active pharmaceutical ingredient (API, i.e. artemether) is investigated as a possible and objective, quantifiable marker for GMP-compliance. First, an analytical UPLC-MS method was developed and verified for artemether, with emphasis on the quantification in the lower concentration range. Second, a swabbing procedure for the outer surface of plastic bottles (powders for suspension) was developed, including a swabbing recovery of the API from the bottle surfaces. Finally, twenty antimalarial samples were investigated. All of them showed some degree of outer contamination; however, large differences in the amount of API contamination between the different samples was observed, ranging between 4 and 144 ng/cm2. A positive correlation was found between the amount of artemether on the packaging and the number of information elements missing on the packaging or leaflet, which was used as one of the tools to evaluate the GMP status of the manufacturer.


Assuntos
Antimaláricos/análise , Artemeter/análise , Cromatografia Líquida/métodos , Embalagem de Medicamentos/normas , Espectrometria de Massas/métodos
18.
Anaesthesia ; 74(7): 868-874, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31049934

RESUMO

We investigated whether low melting point phase-change waxes could be incorporated into emergency drug transport bags to attenuate the known temperature extremes their contents can be exposed to. We exposed two custom-made hollow-walled drug containers placed within a pair of drug transport bags to three day/night cycles including periods of direct radiant sunlight. The wall cavities of one contained air, whereas those of the other contained a paraffin wax (melting point of 44-46 °C) with a high latent heat of fusion (until fully melted, its temperature does not increase further). We collected 25,920 temperature datasets at six locations. We found that 97.8% and 84.7% of ampoule temperatures within the wax and air cavity containers, respectively, were within a target range of 15-40 °C over the study duration (Levene statistic W = 4279.1; Levene's test for equality of variance, p < 0.001). Ampoule temperatures in the wax cavity container only exceeded 40 °C for 1.7% of the time. Even when they did so, their temperature was attenuated to 40.3 °C, despite an ambient air temperature of > 40 °C for 6.4% of the time (peak 46.9 °C) and a bag surface temperature of > 40 °C for 17.2% of the time (peak 64.4 °C). In contrast, the ampoule temperature in the air cavity container exceeded 40 °C for 17.1% of the time (peak 54.1 °C). The latent heat of fusion of phase-change materials may be exploited in the design of drug transport bags to mitigate any temperature changes in the drugs stored within them.


Assuntos
Embalagem de Medicamentos/métodos , Desenho de Equipamento/métodos , Temperatura , Emergências , Ceras
19.
Eur J Pharm Biopharm ; 140: 67-77, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31051250

RESUMO

Prefilled syringes (PFS) constitute a widely used medical device for drug delivery particularly for the drugs of biological origin. Interactions between the product contents and the components of the PFS play a critical role in determining the suitability of selected PFS. A diluent (with benzyl alcohol/BzOH as a preservative) containing PFS used for reconstitution of the lyophilized product revealed a systematic decrease in the BzOH content during accelerated and stress stability program. Investigation was carried out to understand and identify the underlying causes of this phenomenon. BzOH has a varying propensity to bind to the rubber components (stopper and tip-cap) of the PFS. Vapor permeation behavior across the tip-cap of the PFS was studied via headspace-gas chromatography-mass spectroscopy (HS-GC-MS) enabled analysis. Depending on the properties of the rubber components, BzOH can not only bind but also traverse across them, resulting in a systematic loss during the course of the stability. PFS can allow not only water vapor permeation across the tip-cap as shown in previous studies, but also molecules like benzyl alcohol. This phenomenon stresses the need for careful selection of the components of the primary packaging and also provides an opportunity to deploy novel tools like HS-GC-MS in the early selection of the optimal primary packaging configuration.


Assuntos
Vidro/química , Preparações Farmacêuticas/química , Borracha/química , Cromatografia Gasosa/métodos , Sistemas de Liberação de Medicamentos/métodos , Embalagem de Medicamentos/métodos , Excipientes/química , Espectrometria de Massas/métodos , Seringas
20.
Daru ; 27(1): 255-264, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31102140

RESUMO

BACKGROUND: The safe administration of parenteral admixtures should be considered under the headings of physical and chemical stability. Vitamins are considered to be most susceptible to chemical degradation. OBJECTIVES: To evaluate the protective effect of UV-protected monolayer ethylene vinyl acetate (EVA) bags in comparison with that of EVA bags without UV protection, on the physicochemical characteristics and stability of the light sensitive vitamins in pediatric parenteral admixtures stored under various temperature and light conditions. METHODS: Four different parenteral pediatric admixtures (with trace elements and vitamins) in two types of ethylenovinylacetate (EVA) monolayer containers (with - yellow one and without - transparent one UV protection) were assessed. The physicochemical analyses such as visual inspection, pH and potential zeta measurements, lipid globules size distribution and vitamins concentration were performed at 0 h, 24 h, 8 days and 8 days+24 h after the preparation of the TPN admixtures. In order to quantify ascorbic acid, thiamine and pyridoxine levels, HPLC was used. RESULTS: No differences (p < 0.05) in physicochemical stability of TPN admixtures were noted between two types of EVA bags, with the compositions assessed; stored 8 days (4 °C ± 2) without light plus 24 h at room temperature and light exposure. However significant differences were noticed in ascorbic acid, thiamine and pyridoxine content after 8 days+24 h in comparison with t = 0. This was noted for both for UV-protected bags and bags without UV-protection, Nevertheless, amounts were still within the pharmacopeial range. CONCLUSIONS: Both EVA bags under test (with and without UV-protection) ensure physicochemical stability up 8 days at 4 °C ± 2 °C without light exposure and then 24 h at room temperature with light exposure for the total pediatric parenteral admixtures, intended for home parenteral nutrition. Graphical abstract Scheme of physicochemical analysis of parenteral admixtures.


Assuntos
Soluções de Nutrição Parenteral/análise , Polivinil/química , Ácido Ascórbico/análise , Fenômenos Químicos , Criança , Cromatografia Líquida de Alta Pressão , Embalagem de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Humanos , Soluções de Nutrição Parenteral/química , Piridoxina/análise , Tiamina/análise , Raios Ultravioleta
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