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This study was conducted to formulate buccal films consisting of polyvinyl alcohol (PVA) and poly-N-hydroxyethyl-aspartamide (PHEA), to improve the dissolution of the drug through the oral mucosa. Ibuprofen sodium salt was used as a model drug, and the buccal film was expected to enhance its dissolution rate. Two different concentrations of PVA (5% w/v and 7.5% w/v) were used. Solvent casting was used to prepare films, where a solution consisting of drug and polymer was cast and allowed to dry. Attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to investigate the properties of films. In vitro dissolution studies were also conducted to investigate drug release. SEM studies showed that films containing a higher concentration of PVA had larger particles in microrange. FTIR studies confirmed the presence of the drug in films and indicated that ibuprofen sodium did not react with polymers. DSC studies confirmed the crystalline form of ibuprofen sodium when incorporated within films. In vitro dissolution studies found that the dissolution percentage of ibuprofen sodium alone was increased when incorporated within the film from 59 to 74%. This study led to the development of solid microcrystalline dispersion as a buccal film with a faster dissolution rate than the drug alone overcoming problem of poor solubility.
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Ácido Aspártico/química , Poli-Hidroxietil Metacrilato/análogos & derivados , Álcool de Polivinil/química , Amidas/química , Varredura Diferencial de Calorimetria , Cristalização , Liberação Controlada de Fármacos , Ibuprofeno/química , Microscopia Eletrônica de Varredura , Poli-Hidroxietil Metacrilato/química , Polímeros/química , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodosRESUMO
Temperature-controlled, solvent-free centrifugal spinning may be used as a means of rapid production of amorphous solid dispersions in the form of drug-loaded sucrose microfibers. However, due to the high content of amorphous sucrose in the formulations, such microfibers may be highly hygroscopic and unstable on storage. In this study, we explore both the effects of water uptake of the microfibers and the consequences of deliberate recrystallization for the associated dissolution profiles. The stability of sucrose microfibers loaded with three selected BCS class II model drugs (itraconazole (ITZ), olanzapine (OLZ), and piroxicam (PRX)) was investigated under four different relative humidity conditions (11, 33, 53, and 75% RH) at 25 °C for 8 months, particularly focusing on the effect of the highest level of moisture (75% RH) on the morphology, size, drug distribution, physical state, and dissolution performance of microfibers. While all samples were stable at 11% RH, at 33% RH the ITZ-sucrose system showed greater resistance against devitrification compared to the OLZ- and PRX-sucrose systems. For all three samples, the freshly prepared microfibers showed enhanced dissolution and supersaturation compared to the drug alone and physical mixes; surprisingly, the dissolution advantage was largely maintained or even enhanced (in the case of ITZ) following the moisture-induced recrystallization under 75% RH. Therefore, this study suggests that the moisture-induced recrystallization process may result in considerable dissolution enhancement compared to the drug alone, while overcoming the physical stability risks associated with the amorphous state.
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Cristalização/métodos , Água/química , Benzodiazepinas/química , Estabilidade de Medicamentos , Itraconazol/química , Olanzapina , Piroxicam/química , Solubilidade , Sacarose/químicaRESUMO
Nanofibrous systems are attracting increasing interest as a means of drug delivery, although a significant limitation to this approach has been manufacture on a scale commensurate with dosage form production. However, recent work has suggested that nanofibers may be successfully manufactured on a suitable scale using the novel process of pressurized gyration (PG). In this study, we explore the potential of PG as a novel means of generating amorphous solid dispersions of poorly water-soluble drugs with enhanced dissolution performance. We examine the effect of increasing drug loading on fiber properties including size, surface characteristics, and the physical state of both components. Dispersions of ibuprofen in poly(vinylpyrrolidone) (PVP) were prepared (up to 50% w/w loading) and characterized using a range of imaging, thermal, diffraction, and spectroscopic techniques, while the release profiles were studied using sink and non-sink (pH 1.0) conditions. The drug was found to be dispersed on a molecular basis within the fibers; attenuated total reflection FTIR indicated evidence for a direct interaction between the drug and polymer at lower drug loading by the identification of a strong single band in the carbonyl region and amide region of ibuprofen and PVP respectively. Dissolution studies under sink conditions indicated a substantial increase in release rate, while non-sink studies showed evidence for supersaturation. It is concluded that PG presents a viable method for the production of drug-loaded nanofibers for oral administration with enhanced in vitro dissolution rate enhancement.
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Portadores de Fármacos/química , Excipientes/química , Ibuprofeno/química , Nanofibras/química , Polímeros/química , Varredura Diferencial de Calorimetria , Química Farmacêutica , Estabilidade de Medicamentos , Ibuprofeno/administração & dosagem , Pressão , Solubilidade , Água/química , Difração de Raios XRESUMO
A one-pot single-step novel process has been developed to form microbubbles up to 250 µm in diameter using a pressurized rotating device. The microbubble diameter is shown to be a function of rotational speed and working pressure of the processing system, and a modified Rayleigh-Plesset equation has been derived to explain the bubble-forming mechanism. A parametric plot is constructed to identify a rotating speed and working pressure regime, which allows for continuous bubbling. Bare protein (lysozyme) microbubbles generated in this way exhibit a morphological change, resulting in microcapsules over a period of time. Microbubbles prepared with gold nanoparticles at the bubble surface showed greater stability over a time period and retained the same morphology. The functionalization of microbubbles with gold nanoparticles also rendered optical tunability and has promising applications in imaging, biosensing, and diagnostics.
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Ouro/química , Nanopartículas Metálicas/química , MicrobolhasRESUMO
Drug-induced liver injury (DILI) is one of the most common reasons for acute liver failure and a major reason for the withdrawal of medications from the market. There is a growing need for advanced in vitro liver models that can effectively recapitulate hepatic function, offering a robust platform for preclinical drug screening applications. Here, we explore the potential of self-assembling liver spheroids in the presence of electrospun and cryomilled poly(caprolactone) (PCL) nanoscaffolds for use as a new preclinical drug screening tool. This study investigated the extent to which nanoscaffold concentration may have on spheroid size and viability and liver-specific biofunctionality. The efficacy of our model was further validated using a comprehensive dose-dependent acetaminophen toxicity protocol. Our findings show the strong potential of PCL-based nanoscaffolds to facilitate in situ self-assembly of liver spheroids with sizes under 350 µm. The presence of the PCL-based nanoscaffolds (0.005 and 0.01% w/v) improved spheroid viability and the secretion of critical liver-specific biomarkers, namely, albumin and urea. Liver spheroids with nanoscaffolds showed improved drug-metabolizing enzyme activity and greater sensitivity to acetaminophen compared to two-dimensional monolayer cultures and scaffold-free liver spheroids. These promising findings highlight the potential of our nanoscaffold-based liver spheroids as an in vitro liver model for drug-induced hepatotoxicity and drug screening.
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Acetaminofen , Avaliação Pré-Clínica de Medicamentos , Fígado , Esferoides Celulares , Alicerces Teciduais , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Acetaminofen/química , Acetaminofen/farmacologia , Humanos , Alicerces Teciduais/química , Fígado/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/patologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Poliésteres/química , Sobrevivência Celular/efeitos dos fármacos , AnimaisRESUMO
Telemedicine is defined as the delivery of healthcare services at a distance using electronic means. The incorporation of 3D printing in the telemedicine cycle could result in pharmacists designing and manufacturing personalised medicines based on the electronic prescription received. Even with the advantages of telemedicine, numerous barriers to the uptake hinder the wider uptake. Of particular concern is the cyber risk associated with the remote digital transfer of the computer-aided design (CAD) file (acting as the electronic prescription) to the 3D printer and the reproducibility of the resultant printed medicinal products. This proof-of-concept study aimed to explore the application of secure remote 3D printing of model solid dosage forms using the patented technology, DEFEND3D, which is designed to enhance cybersecurity and intellectual property (IP) protection. The size, shape, and colour of the remote 3D-printed model medicinal products were also evaluated to ensure the end-product quality was user-focused. Thermoplastic polyurethane (TPU) and poly(lactic) acid (PLA) were chosen as model polymers due to their flexibility in preventing breakage printing and ease of printing with fused deposition modelling (FDM). Our work confirmed the potential of secure remote 3D (FDM) printing of prototype solid dosage forms resulting in products with good reproducibility, resolution, and quality towards advancements in telemedicine and digital pharmacies. The limitation of the work presented here was the use of model polymers and not pharmaceutically relevant polymers. Further work could be conducted using the same designs chosen in this study with pharmaceutically relevant polymers used in hot-melt extrusion (HME) with shown suitability for FDM 3D printing. However, it should be noted that any challenges that may occur with pharmaceutically relevant polymers are likely to be related to the polymer's printability and printer choice as opposed to the ability of the CAD file to be transferred to the printer remotely.
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Substandard and falsified (SF) medicines are a global health challenge with the World Health Organization (WHO) estimating that 1 in 10 of medicines in low- and middle-income countries (LMICs) are SF. Antimicrobials (i.e. antimalarials, antibiotics) are the most commonly reported SF medicines. SF medicines contribute significantly to the global burden of infectious diseases and antimicrobial resistance (AMR). This article discusses the challenges associated with the global impact of SF and unregistered/unlicensed antimicrobials with a focus on anti-TB medicines. Tuberculosis (TB) is the 13th leading cause of death worldwide, and is currently the second leading cause of death from a single infectious agent, ranking after COVID-19 and above HIV/AIDS. Specifically in the case of TB, poor quality of anti-TB medicines is among the drivers of the emergence of drug-resistant TB pathogens. In this article, we highlight and discuss challenges including the emergence of SF associated AMR, patient mistrust and lack of relevant data. We also present study reports to inform meaningful change. Recommended solutions involve the adaptation of interventions from high-income countries (HICs) to LMICS, the need for improvement in the uptake of medication authentication tools in LMICs, increased stewardship, and the need for global and regional multidisciplinary legal and policy cooperation, resulting in improved legal sanctions.
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Plant-mediated green synthesis is a cost-effective and eco-friendly process used to synthesize metallic nanoparticles. Experimental pH is of interest due to its ability to influence nanoparticle size and shape; however, little has been explored in comparison to the influence of this parameter on the therapeutic potential of resultant metallic nanoparticles. Our work investigated the influence of pH alternation on antimicrobial properties of plant-mediated green synthesized (using Spinacia oleracea leaf extract) silver nanoparticles. We further investigated if the antimicrobial activity was sustained at 8 weeks (after initial green synthesis). Antimicrobial properties were evaluated against Escherichia coli, Staphylococcus aureus, and Candida albicans. Our work confirmed that experimental pH in plant-mediated green synthesis of silver nanoparticles influenced their resultant antimicrobial properties. Silver nanoparticles generated at experimental pH 4,5, and nine showed activity against E. coli which was sustained at various levels over 8 weeks. No antimicrobial activity was observed against S. aureus, and weak antimicrobial activity against C. albicans. These interesting findings highlight the importance of experimental pH. Further understanding of the role experimental pH plays on resultant metallic nanoparticle properties as it relates to biological and therapeutic impact is required, which will have an impact on wider applications beyond antimicrobial activity.
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Simultaneous expansion of the Internet and increased globalisation of the pharmaceutical industry have meant medication can be accessed transnationally from both legal and illicit sources. This has coincided with the rise of substandard and falsified medicines (SFMs) online. These products fail to meet regulatory or quality standards and/or are constituted with substandard ingredients, causing undesired pharmacological effects, including possible injury and death. This review aimed to identify original research studies that examined characteristics of SFM online sales, attitudes towards purchasing medicines online and strategies to address this drug safety challenge. Keywords of 'Substandard' and 'Falsified'/'Counterfeit' and 'Medicines'/'Drugs' and 'Online'/'Internet' were searched using Web of Knowledge and PubMed databases. Resulting literature, which satisfied the study's inclusion criteria, was included in the review, and the findings from each paper were assessed. From an initial 185 literature articles, 7 were eligible according to the inclusion criteria to be reviewed. These articles identified studies testing SFMs purchased online, surveys of attitudes and knowledge about SFMs online, and website content analysis to detect illegal online sales. Challenges identified were lack of knowledge and awareness among consumers and physicians, in addition to the use of direct-to-consumer-advertising, via Internet platforms and social media, providing easy access to SFMs. Despite this, medicine authentication technology, website verification approaches and new detection methods were identified as potential solutions specific to online SFM sales. To address online sales of SFMs, more robust research, greater awareness/educational programmes, analytical detection methods and more stringent online global governance are required.
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OBJECTIVES: Cancer and malaria both have high incidence rates and are leading causes of mortality worldwide, especially in low and middle-income countries with reduced access to the quality healthcare. The objective of this critical review was to summarize key associations and new perspectives between the two diseases as is reported in existing literature. METHODS: A critical review of research articles published between 1st January 2000 - 1st July 2020 which yielded 1753 articles. These articles were screened based on a precise inclusion criteria. Eighty-nine eligible articles were identified and further evaluated. RESULTS: Many articles reported anti-cancer activities of anti-malarial medicines, including Artemisinin and its derivatives. Other articles investigated the use of chemotherapy in areas burdened by malaria, treatment complications that malaria may cause for cancer patients as well as ways to circumvent cancer related drug resistance. Potential novel targets for cancer treatment, were identified namely oncofoetal chondroitin sulphate and haem, as well as the use of circumsporozoite proteins. A number of articles also discussed Burkitt lymphoma or febrile neutropenia. CONCLUSIONS: Overall, excluding for Burkitt lymphoma, the relationship between cancer and malaria requires further extensive research in order to define association. There great potential promising new novel anti-cancer therapies using anti-malarial drugs. Created using BioRender.
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Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great variability in its physical-chemical properties and is a basis for its broad successful application in pharmaceutical research, development, and manufacturing. The excellent mucoadhesive properties of HPMC predetermine its use in oromucosal delivery systems including mucoadhesive tablets and films. HPMC also possesses desirable properties for formulating amorphous solid dispersions increasing the oral bioavailability of poorly soluble drugs. Printability and electrospinnability of HPMC are promising features for its application in 3D printed drug products and nanofiber-based drug delivery systems. Nanoparticle-based formulations are extensively explored as antigen and protein carriers for the formulation of oral vaccines, and oral delivery of biologicals including insulin, respectively. HPMC, being a traditional pharmaceutical excipient, has an irreplaceable role in the development of new pharmaceutical technologies, and new drug products leading to continuous manufacturing processes, and personalized medicine. This review firstly provides information on the physical-chemical properties of HPMC and a comprehensive overview of its application in traditional oral drug formulations. Secondly, this review focuses on the application of HPMC in modern pharmaceutical technologies including spray drying, hot-melt extrusion, 3D printing, nanoprecipitation and electrospinning leading to the formulation of printlets, nanoparticle-, microparticle-, and nanofiber-based delivery systems for oral and oromucosal application. Hypromellose is an excellent excipient for formulation of classical dosage forms and advanced drug delivery systems. New methods of hypromellose processing include spray draying, hot-melt extrusion, 3D printing, and electrospinning.
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Excipientes , Tecnologia Farmacêutica , Composição de Medicamentos , Liberação Controlada de Fármacos , Derivados da Hipromelose , Solubilidade , Comprimidos , ViscosidadeRESUMO
Biologics have changed the management of Inflammatory Bowel Disease (IBD), but there are concerns regarding unexpected systemic toxicity and loss of therapeutic response following administration by injection. Local delivery of biologics directly to the inflamed mucosa via rectal enema administration addresses the problems associated with systemic administration. Hydrogels are potentially useful delivery vehicles enabling rectal administration of biologics. Here, we prepared a hydrogel system based on methylcellulose (MC) and hyaluronic acid (HA), which possesses mucosal healing properties, incorporating a model macromolecular drug, namely (fluorescently-labeled) bovine serum albumin (BSA). The BSA-loaded MCHA hydrogel showed temperature-dependent gelation (liquid-like at 20 °C and gel-like at 37 °C) and shear thinning behavior, with these being important and desirable characteristics for rectal application (enabling easy application and retention). BSA release from the MCHA system at 37 °C was linear, with 50% of the loaded drug released within 2 h. The system demonstrated acceptable toxicity towards intestinal (colon) Caco-2 epithelial cells, even at high concentrations. Importantly, application of the BSA-loaded MCHA hydrogel to polarized Caco-2 monolayers, with or without an exemplar absorption enhancer, resulted in transintestinal permeability of BSA. The study therefore indicates that the MCHA hydrogel shows potential for topical (rectal) delivery of biologics in IBD.
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With the well-known advantages of additive manufacturing methods such as three-dimensional (3D) printing in drug delivery, it is disappointing that only one product has been successful in achieving regulatory approval in the past few years. Further research and development is required in this area to introduce more 3D printed products into the market. Our study investigates the potential of fixed dose combination solid dispersion drug products generated via 3D printing. Two model drugs-fluorescein sodium (FS) and 5-aminosalicyclic acid (5-ASA)-were impregnated onto a polyvinyl alcohol (PVA) filament, and the influence of solvent choice in optimal drug loading as well as other influences such as the physicochemical and mechanical properties of the resultant filaments were investigated prior to development of the resultant drug products. Key outcomes of this work included the improvement of filament drug loading by one- to threefold due to solvent choice on the basis of its polarity and the generation of a 3D-printed product confirmed to be a solid dispersion fixed dose combination with the two model drugs exhibiting favourable in vitro dissolution characteristics.
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Poor aqueous solubility (<0.1 mg/mL) affects a significant number of drugs currently on the market or under development. Several formulation strategies including salt formation, particle size reduction, and solid dispersion approaches have been employed with varied success. In this review, we focus primarily on the emerging trends in the generation of amorphous and micro/nano-crystalline solid dispersions using electrospinning to improve the dissolution rate and in turn the bioavailability of poorly water-soluble drugs. Electrospinning is a simple but versatile process that utilizes electrostatic forces to generate polymeric fibers and has been used for over 100 years to generate synthetic fibers. We discuss the various electrospinning studies and spinneret types that have been used to generate amorphous and crystalline solid dispersions.
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Recent evidence has continued to support the applicability of progesterone in preventing preterm birth, hence the development of an appropriate vaginal delivery system for this drug would be of considerable interest. Here, we describe the development of progesterone-loaded bioadhesive nanofibers using pressurized gyration for potential incorporation into a vaginal insert, with a particular view to addressing the challenges of incorporating a poorly water-soluble drug into a hydrophilic nanofiber carrier. Polyethylene oxide and carboxymethyl cellulose were chosen as polymers to develop the carrier systems, based on previous evidence of their yielding mucoadhesive nanofibers using the pressurized gyration technique. The fabrication parameters such as solvent system, initial drug loading and polymer composition were varied to facilitate optimisation of fiber structure and efficiency of drug incorporation. Such studies resulted in the formation of nanofibers with satisfactory surface appearance, diameters in the region of 400â¯nm and loading of up to 25% progesterone. Thermal and spectroscopic analyses indicated that the drug was incorporated in a nanocrystalline state. Release from the drug-loaded fibers indicated comparable rates of progesterone dissolution to that of Cyclogest, a commercially available progesterone pessary, allowing release over a period of hours. Overall, the study has shown that pressurized gyration may produce bioadhesive progesterone-loaded nanofibers which have satisfactory loading of a poorly water-soluble drug as well as having suitable structural and release properties. The technique is also capable of producing fibers at a yield commensurate with practical applicability, hence we believe that the approach shows considerable promise for the development of progesterone dosage forms for vaginal application.
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Carboximetilcelulose Sódica/química , Portadores de Fármacos , Nanofibras , Polietilenoglicóis/química , Nascimento Prematuro/prevenção & controle , Progesterona/administração & dosagem , Progesterona/química , Progestinas/administração & dosagem , Progestinas/química , Tecnologia Farmacêutica/métodos , Adesividade , Administração Intravaginal , Cristalografia por Raios X , Composição de Medicamentos , Liberação Controlada de Fármacos , Feminino , Humanos , Nanomedicina , Gravidez , Nascimento Prematuro/etiologia , Nascimento Prematuro/fisiopatologia , Pressão , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Propriedades de SuperfícieRESUMO
Mucoadhesive delivery systems have attracted remarkable interest recently, especially for their potential to prolong dosage form resident times at sites of application such as the vagina or nasal cavity, thereby improving convenience and compliance as a result of less frequent dosage. Mucoadhesive capabilities need to be routinely quantified during the development of these systems. This is however logistically challenging due to difficulties in obtaining and preparing viable mucosa tissues for experiments. Utilizing artificial membranes as a suitable alternative for quicker and easier analyses of mucoadhesion of these systems is currently being explored. In this study, the mucoadhesive interactions between progesterone-loaded fibers (with varying carboxymethyl cellulose (CMC) content) and either artificial (cellulose acetate) or mucosa membranes are investigated by texture analysis and results across models are compared. Mucoadhesion to artificial membrane was about 10 times that of mucosa, though statistically significant ( p = 0.027) association between the 2 data sets was observed. Furthermore, a hypothesis relating fiber-mucosa interfacial roughness (and unfilled void spaces on mucosa) to mucoadhesion, deduced from some classical mucoadhesion theories, was tested to determine its validity. Points of interaction between the fiber and mucosa membrane were examined using atomic force microscopy (AFM) to determine the depths of interpenetration and unfilled voids/roughness, features crucial to mucoadhesion according to the diffusion and mechanical theories of mucoadhesion. A Kendall's tau and Goodman-Kruskal's gamma tests established a monotonic relationship between detaching forces and roughness, significant with p-values of 0.014 and 0.027, respectively. A similar relationship between CMC concentration and interfacial roughness was also confirmed. We conclude that AFM analysis of surface geometry following mucoadhesion can be explored for quantifying mucoadhesion as data from interfacial images correlates significantly with corresponding detaching forces, a well-established function of mucoadhesion.
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Progesterona/química , Sistemas de Liberação de Medicamentos , Mucosa , Nanofibras , Preparações FarmacêuticasRESUMO
BACKGROUND: Compliance aids are devices which have been developed and are currently used to assist individuals in their medicines management. The use of compliance aids involves the transfer of medicines from the manufacturers' original packaging and repackaged into an multicompartment compliance aid (MCA). MCAs do not guarantee the same level of protection compared to manufacturer's original packaging. OBJECTIVE: The aim of this study was to investigate the stability profile of atenolol, aspirin and lansoprazole dosage forms repackaged together in two different commercially available MCAs. METHODS: In a laboratory in the United Kingdom, the physical stability of the formulations repackaged into two commercially available brands of MCAs was evaluated. After 8 weeks of storage (under controlled ambient conditions), changes in the disintegration (tablets only) and dissolution properties (all formulations) were examined in accordance with British Pharmacopoeia (BP) specifications. KEY FINDINGS: Findings from this study confirm that changes in solid-dosage form quality are observed when repackaged into MCAs compared to manufacturers packaging resulting in differences in in-vitro dissolution performance. However, even with these changes, overall product performance was acceptable and within BP specifications. CONCLUSION: There is a need for greater collaboration in this area between manufacturers, hospital and community pharmacists, academics and policymakers to increase the data available on the physical stability and in turn performance of medicines repackaged into MCAs.
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In this study, we evaluate the dissolution rate enhancement of solid microcrystalline dispersion (SMD) films of olanzapine (OLZ) formulated with four water-soluble polymers namely poly(N-vinylpyrrolidone) (PVP), poloxamer 188 (P188), poloxamer 407 (P407) and Soluplus(®) (SLP). Prepared formulations were characterised to determine particle size, morphology, hydrogen bonding interactions, thermal characteristics as well as in vitro dissolution studies conducted under sink conditions (pH 6.8). Particle size of OLZ in all formulations ranged between 42 and 58µm. Attenuated Total Reflectance Fourier Transform Infrared spectroscopy (ATR-FTIR), Differential Scanning Calorimetry (DSC) and Hot-Stage Microscopy (HSM) studies confirmed OLZ was well maintained in its crystalline state during the formulation process. In vitro dissolution studies showed immediate drug release from all formulation when compared to the drug alone. The greatest increase in in vitro dissolution rate was observed in formulations containing P188 most likely due to its enhanced hydrophilic and surfactant properties compared to the other agents used. Overall, this study successfully generated OLZ loaded SMD films with improved in vitro dissolution rates which is highly likely to result in improved oral bioavailability in vivo.
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Benzodiazepinas/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Poloxâmero/química , Polietilenoglicóis/química , Polivinil/química , Pirrolidinonas/química , Benzodiazepinas/farmacocinética , Cristalização , Ligação de Hidrogênio , Olanzapina , Tamanho da Partícula , SolubilidadeRESUMO
Solid dispersion technology represents a successful approach to addressing the bioavailability issues caused by the low aqueous solubility of many Biopharmaceutics Classification System (BCS) Class II drugs. In this study, the use of high-yield manufacture of fiber-based dispersion is explored as an alternative approach to monolith production methods. A temperature-controlled solvent-free centrifugal spinning process was used to produce sucrose-based microfibers containing the poorly water-soluble drugs olanzapine and piroxicam (both BCS Class II); these were successfully incorporated into the microfibers and the basic characteristics of fiber diameter, glassy behavior, drug loading capacity and drug-sucrose interaction assessment were measured. Scanning electron microscopy revealed that bead-free drug-loaded microfibers with homogenous morphology and diameter in the range of a few micrometers were prepared using our process. Differential scanning calorimetric and X-ray diffraction analyses showed that both drug and carrier were present in the amorphous state in the microfibers, although in the case of piroxicam-loaded microfibers, the presence of small amounts of crystalline drug was observed under polarized light microscopy and in Fourier transform infrared spectra. Drug dissolution performance was evaluated under both sink and non-sink conditions and was found to be significantly enhanced compared to the corresponding crystalline physical mixtures and pure drugs, with evidence of supersaturation behavior noted under non-sink conditions. This study has demonstrated that microfiber-based dispersions may be manufactured by the centrifugal spinning process and may possess characteristics that are favorable for the enhanced dissolution and oral absorption of drugs.
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Benzodiazepinas/química , Centrifugação , Sacarose/química , Temperatura , Calibragem , Varredura Diferencial de Calorimetria , Microscopia Eletrônica de Varredura , Olanzapina , Difração de Pó , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Água/químicaRESUMO
PLAIN ENGLISH SUMMARY: A one day public engagement workshop was held to focus on the priorities of older people about research and practice in health and social care. Seventy-five older people from the general public and a variety of backgrounds attended this event to share their views and discuss what should be prioritised. The main aim of this workshop was to identify and prioritise issues that are important to older people that would benefit from further research, as well as create an environment for older people to share ideas and problems related to these important issues. Key priorities brought up by participants included loneliness and isolation, support and training for professional and family carers, post-surgical care, negative perceptions of older people and inequalities related to public services and healthcare. Participants further suggested older people should be actively involved in all stages of the research process. ABSTRACT: As the world's population ages, there is an increasing need for research that addresses the priorities of older people. A public engagement workshop focusing on the priorities of older people for research and practice in health and social care was attended by seventy-five people aged 70 years and above in London, United Kingdom (UK). The workshop aimed to identify and prioritise issues important to older people that would benefit from further research and act as a platform to promote sharing of ideas and problems related to these important issues. Key priorities emerged including loneliness and isolation, support and training for professional and family carers, post-surgical care, negative perceptions of older people and inequalities related to public services and healthcare. Participants further suggested older people should be actively involved in all stages of the research process.