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1.
Explor Res Clin Soc Pharm ; 12: 100380, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38146320

RESUMO

Background: Extemporaneous compounding is practiced globally by pharmacists to allow for dispensing of personalised doses of medicinal products not commercially available. Extemporaneous compounding must result in a product which is safe and effective. However, data on formulation and expiry of extemporaneous products may not be readily available. Pharmacists access various resources including compounding databases to obtain information on composition, preparation, and expiry of extemporaneous preparations. Objectives: The aim of this study was to evaluate the type and frequency of extemporaneous compounding in hospital and community pharmacies in the Republic of Ireland (ROI) and to obtain contemporary information on compounding practices and resources used. Methods: All community and hospital pharmacists registered with the Pharmaceutical Society of Ireland, were invited to participate in an on-line survey. The study was approved by the Royal College of Surgeons in Ireland (RCSI) research ethics committee. Results: A total of 202 pharmacists responded to the survey, of which 145 were community-based, 52 hospital-based, and 5 practicing in both. On average, hospital and community pharmacists (n = 138) dispensed <2-10 prescriptions for extemporaneous products per month. Pharmacists reported compounding 13 different types of extemporaneous preparations. Of these, dermatological preparations and oral liquid formulations (OLFs) were most commonly compounded. Extemp.ie, an Irish compounding database, was the most frequently used resource for compounding guidance and product expiry. Conclusions: The results of this study show that extemporaneous compounding is still practiced in hospital and community pharmacies in the ROI. The limited response of 4.6% obtained may reflect that extemporaneous compounding is concentrated in a relatively small number of pharmacies. There remains a clinical need for extemporaneous products in the ROI and extemporaneous compounding continues to be an invaluable skillset for pharmacists.

2.
Eur J Pharm Sci ; 183: 106379, 2023 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36646154

RESUMO

BACKGROUND AND AIMS: Anti-TNF biological therapies such as infliximab (INF) have revolutionised the treatment of inflammatory bowel diseases (IBD). However, serious adverse effects due to systemic administration can significantly impact patient quality of life, limiting their success. Oral nanomedicines propose an innovative solution to provide local delivery to inflamed gastrointestinal tissues, thereby limiting systemic exposure and enhancing therapeutic efficacy. This study aimed to examine the potential of INF nanomedicines for IBD treatment with a focus on nanoparticle (NP) size to modulate the targeting of INF to the epithelial barrier. METHODS: Healthy and inflamed in vitro models of the intestinal epithelial barrier were established to examine the cell interaction of PLGA-PEGNPs of varying particle sizes and polydispersities. INF-loaded NPs were prepared by electrostatic interaction of INF with NPs and examined for their therapeutic efficacy in the inflamed epithelial cell barrier model. RESULTS: NP interaction was significantly enhanced in the inflamed cell barrier model, with increased transport observed for 130 - 300 nm NPs and accumulation of larger NPs (∼600 nm) at the barrier. Delivery of INF directly to the inflamed barrier by ∼600 nm NPs accelerated recovery of barrier integrity and reduced inflammatory cytokine secretion and cytotoxicity in comparison to treatment with INF alone. CONCLUSIONS: Results from this study show that NP particle size can be used to differentially target and treat the inflamed intestinal barrier. Oral INF nanomedicines of modulated size present a novel strategy for the local, targeted treatment of IBD.


Assuntos
Doenças Inflamatórias Intestinais , Nanopartículas , Humanos , Infliximab , Nanomedicina , Qualidade de Vida , Inibidores do Fator de Necrose Tumoral , Mucosa Intestinal , Portadores de Fármacos
3.
Molecules ; 26(2)2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33435555

RESUMO

Extemporaneous oral liquid preparations are commonly used when there is no commercially available dosage form for adjustable dosing. In most cases, there is a lack of stability data to allow for an accurately assigned shelf life and storage conditions to give greater confidence of product safety and efficacy over its shelf life. The aim of this study was to evaluate the physical, chemical and microbiological stability of an extemporaneous oral liquid suspension of losartan potassium, 5 mg/mL, used to treat paediatric hypertension in Our Lady's Children's Hospital Crumlin, Ireland. The losartan content of extemporaneous oral suspensions, prepared with and without addition of water, was measured by UV and confirmed by HPLC analysis. Suspensions were stored at 4 °C and room temperature (RT) and were monitored for changes in; pH, colour, odour, re-dispersibility, Total Aerobic Microbial Count, Total Yeast and Mould Count and absence of E. coli. Results showed that suspensions prepared by both methods, stored at 4 °C and RT, were physically and microbiologically stable over 28 days. Initial losartan content of all suspensions was lower than expected at 80-81% and did not change significantly over the 28 days. HPLC and NMR did not detect degradation of losartan in the samples. Suspensions prepared in water showed 100% losartan content. The reduced initial losartan content was confirmed by HPLC and was related to the acidic pH of the suspension vehicle. Physiochemical properties of the drug are important factors for consideration in the selection of suspension vehicle for extemporaneous compounding of oral suspensions as they can influence the quality, homogeneity and efficacy of these preparations.


Assuntos
Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/química , Bactérias/efeitos dos fármacos , Losartan/administração & dosagem , Losartan/química , Comprimidos/química , Administração Oral , Composição de Medicamentos , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Suspensões
4.
Int J Mol Sci ; 21(24)2020 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-33352749

RESUMO

The expansion of nanotechnology for drug delivery applications has raised questions regarding the safety of nanoparticles (NPs) due to their potential for interacting at molecular and cellular levels. Although polymeric NPs for drug delivery are formulated using FDA-approved polymers such as lactide- and glycolide-based polymers, their interactions with blood constituents, remain to be identified. The aim of this study was to determine the impact of size-selected Poly-lactide-co-glycolide-polyethylene glycol (PLGA-PEG) NPs on platelet activity. The NPs of 113, 321, and 585 nm sizes, were formulated and their effects at concentrations of 0-2.2 mg/mL on the activation and aggregation of platelet-rich plasma (PRP) were investigated. The results showed that NPs of 113 nm did not affect adenosine diphosphate (ADP)-induced platelet aggregation at any NP concentration studied. The NPs of 321 and 585 nm, at concentrations ≥0.25 mg/mL, reduced ADP-activated platelet aggregation. The platelet activation profile remained unchanged in the presence of investigated NPs. Confocal microscopy revealed that NPs were attached to or internalised by platelets in both resting and activated states, with no influence on platelet reactivity. The results indicate minimal risks of interference with platelet function for PLGA-PEG NPs and that these NPs can be explored as nanocarriers for targeted drug delivery to platelets.


Assuntos
Plaquetas/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Nanopartículas/administração & dosagem , Agregação Plaquetária/efeitos dos fármacos , Plasma Rico em Plaquetas/efeitos dos fármacos , Polietilenoglicóis/química , Copolímero de Ácido Poliláctico e Ácido Poliglicólico/química , Plaquetas/fisiologia , Portadores de Fármacos/química , Humanos , Nanopartículas/química , Agregação Plaquetária/fisiologia , Plasma Rico em Plaquetas/fisiologia
5.
Pharmaceutics ; 12(11)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33228175

RESUMO

Oral nanomedicines are being investigated as an innovative strategy for targeted drug delivery to treat inflammatory bowel diseases. Preclinical studies have shown that nanoparticles (NPs) can preferentially penetrate inflamed intestinal tissues, allowing for targeted drug delivery. NP size is a critical factor affecting their interaction with the inflamed intestinal barrier and this remains poorly defined. In this study we aimed to assess the impact of NP particle size (PS) and polydispersity (PDI) on cell interaction and uptake in an inflamed epithelial cell model. Using 10, 55 and 100 mg/mL poly(lactic-co-glycolic acid)-polyethylene glycol (PLGA-PEG), NPs of 131, 312 and 630 nm PS, respectively, were formulated by solvent dispersion. NP recovery was optimised by differential centrifugation to yield NPs of decreased and unimodal size distribution. NP-cell interaction was assessed in healthy and inflamed caco-2 cell monolayers. Results show that NP interaction with caco-2 cells increased with increasing PS and PDI and was significantly enhanced in inflamed cells. Trypan blue quenching revealed that a significant proportion of multimodal NPs were primarily membrane bound, while monomodal NPs were internalized within cells. These results are interesting as the PS and PDI of NPs can be optimised to allow targeting of therapeutic agents to the epithelial membrane and/or intracellular targets in the inflamed intestinal epithelium.

6.
Pharmaceutics ; 11(10)2019 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-31590303

RESUMO

Nanotechnology is being increasingly utilised in medicine as diagnostics and for drug delivery and targeting. The small size and high surface area of nanoparticles (NPs), desirable properties that allow them to cross biological barriers, also offer potential for interaction with other cells and blood constituents, presenting possible safety risks. While NPs investigated are predominantly based on the biodegradable, biocompatible, and FDA approved poly-lactide-co-glycolide (PLGA) polymers, pro-aggregatory and antiplatelet effects have been reported for certain NPs. The potential for toxicity of PLGA based NPs remains to be examined. The aims of this study were to determine the impact of size-selected PLGA-PEG (PLGA-polyethylene glycol) NPs on platelet activation and aggregation. PLGA-PEG NPs of three average sizes of 112, 348, and 576 nm were formulated and their effect at concentrations of 0.0-2.2 mg/mL on the activation and aggregation of washed human platelets (WP) was examined. The results of this study show, for the first time, NPs of all sizes associated with the surface of platelets, with >50% binding, leading to possible internalisation. The NP-platelet interaction, however, did not lead to platelet aggregation nor inhibited aggregation of platelets induced by thrombin. The outcome of this study is promising, suggesting that these NPs could be potential carriers for targeted drug delivery to platelets.

7.
Int J Pharm ; 565: 533-542, 2019 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-31085256

RESUMO

In this study we examined the potential of novel biodegradable polymers of polyesterurethane (PU), and its PEGylated (PU-PEG) form as nanocarriers of Infliximab (INF), to treat inflammation in an in-vitro epithelial model. Nanoparticles (NPs) formulated were of average size of 200-287 nm. INF loading of NPs (INF-NPs) resulted in an increase in size and zeta potential. No cytotoxicity was observed for any of the NPs. Cellular interaction and uptake of PU NPs were similar compared with polycaprolactone (PCL) NPs and significantly higher to Poly(lactic-co-glycolic) acid (PLGA) NPs. Cellular interaction was higher for corresponding PEG-NPs. INF-PU and INF-PU-PEG NPs showed a rapid rate and extent of recovery of the epithelial barrier function in inflamed Caco-2 cell monolayers and decreased cytokine levels in inflamed monocytes. Results obtained in this study are promising and the potential of PU and PU-PEG NPs for drug delivery and targeting to treat gastrointestinal inflammation warrants further investigation.


Assuntos
Anti-Inflamatórios/administração & dosagem , Portadores de Fármacos/administração & dosagem , Infliximab/administração & dosagem , Nanopartículas/administração & dosagem , Poliuretanos/administração & dosagem , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Humanos , Interleucina-8/imunologia , Mucosa Intestinal/metabolismo , Lipopolissacarídeos , Monócitos/efeitos dos fármacos , Monócitos/imunologia , Fator de Necrose Tumoral alfa/imunologia
8.
Scand J Gastroenterol ; 54(1): 18-26, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30678499

RESUMO

There have been major advancements in the treatment of inflammatory bowel disease (IBD) over the past three decades. However despite significant progress, the best available treatments continue to demonstrate variable efficacy in patients and are associated with adverse effects. Therefore there remains an unmet clinical need for ongoing therapeutic advances for IBD. In recent years nanomedicines have emerged as promising diagnostic and therapeutic tools. Nanoparticles in particular show promise to facilitate targeted oral drug delivery in IBD. Here we discuss the pitfalls of current therapies and explore the potential for nanoparticles to improve the treatment of IBD. This review examines the range of conventional and novel therapies which have benefited from nanoparticle-mediated delivery and highlights the proven therapeutic efficacy of this approach in preclinical models. These strategies under development represent a novel and innovative treatment for IBD.


Assuntos
Sistemas de Liberação de Medicamentos , Fármacos Gastrointestinais/administração & dosagem , Doenças Inflamatórias Intestinais/tratamento farmacológico , Nanomedicina/tendências , Administração Oral , Animais , Modelos Animais de Doenças , Fármacos Gastrointestinais/química , Humanos , Nanopartículas
9.
Curr Pharm Biotechnol ; 17(10): 905-14, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27194359

RESUMO

The influence of thermal and shear stressors on the stability of the anti-TNF-α monoclonal antibody (mAb), Infliximab® (INF) was investigated. INF at concentrations of 1, 4 and 10 mg/ml was subjected to thermal stress at temperatures of 25-65°C and to shear force by sonication for 1 and 3 minutes. The stressed samples were analysed for physical properties by particle size, zeta potential, for structural integrity by gel electrophoresis (SDS-PAGE) and circular dichroism, INF content by UV spectroscopy and for biological activity by ELISA. Results show no change in physical properties or structural integrity of INF at any concentration tested, when subjected to a temperature of up to 50°C. At 65°C, aggregation and precipitation of INF was observed. When subjected to shear stress, higher concentrations of INF at 4 and 10mg/ml maintained their physical properties and structural integrity. However, the biological activity of INF was found to decrease with increasing temperature and sonication time, and was concentration dependent (ANOVA; p<0.05). Interestingly, lyophilisation of INF at 1mg/ml did not affect its physical properties, structural integrity or its biological activity. These findings have important implications with respect to pharmaceutical processing of INF and mAbs including formulation as polymeric micro and nanoparticle systems for sustained or targeted delivery. These findings also have important implications with respect to the handling and storage of INF and mAbs for clinical use.


Assuntos
Anticorpos Monoclonais/química , Temperatura Alta , Infliximab/química , Dicroísmo Circular , Relação Dose-Resposta a Droga , Estabilidade de Medicamentos , Armazenamento de Medicamentos , Eletroforese em Gel de Poliacrilamida , Liofilização , Humanos , Tamanho da Partícula , Resistência ao Cisalhamento , Estresse Mecânico , Fator de Necrose Tumoral alfa
10.
Eur J Pharmacol ; 780: 53-64, 2016 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-26997367

RESUMO

Deregulation of the ubiquitin-proteasome pathway has been frequently observed in a number of malignancies. Using quantitative Western blotting of normal and matched tumour tissue, we here identified a significant increase in the 19S proteasome subunit Rpt4 in response to chemoradiation in locally advanced rectal cancer patients with unfavourable outcome. We therefore explored the potential of Rpt4 reduction as a therapeutic strategy in colorectal cancer (CRC). Utilizing siRNA to down regulate Rpt4 expression, we show that silencing of Rpt4 reduced proteasomal activity and induced endoplasmic reticulum stress. Gene silencing of Rpt4 also inhibited cell proliferation, reduced clonogenic survival and induced apoptosis in HCT-116 colon cancer cells. We next developed a cell penetrating peptide-based nanoparticle delivery system to achieve in vivo gene silencing of Rpt4. Administration of Rpt4 siRNA nanoparticles reduced tumour growth and improved survival in a HCT-116 colon cancer xenograft tumour model in vivo. Collectively, our data suggest that inhibition of Rpt4 represents a novel strategy for the treatment of CRC.


Assuntos
Neoplasias Colorretais/enzimologia , Neoplasias Colorretais/terapia , Terapia de Alvo Molecular , Complexo de Endopeptidases do Proteassoma/metabolismo , Apoptose/genética , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Portadores de Fármacos/química , Estresse do Retículo Endoplasmático/genética , Regulação Neoplásica da Expressão Gênica/genética , Técnicas de Silenciamento de Genes , Inativação Gênica , Células HCT116 , Humanos , Nanopartículas/química , Complexo de Endopeptidases do Proteassoma/deficiência , Complexo de Endopeptidases do Proteassoma/genética , RNA Interferente Pequeno/química , RNA Interferente Pequeno/genética , Falha de Tratamento
11.
Mater Sci Eng C Mater Biol Appl ; 59: 249-257, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26652371

RESUMO

Localised controlled release of simvastatin from porous freeze-dried chitosan-gelatin (CH-G) scaffolds was investigated by incorporating simvastatin loaded poly-(dl-lactide-co-glycolide) acid (PLGA) microparticles (MSIMs) into the scaffolds. MSIMs at 10% w/w simvastatin loading were prepared using a single emulsion-solvent evaporation method. The MSIM optimal amount to be incorporated into the scaffolds was selected by analysing the effect of embedding increasing amounts of blank PLGA microparticles (BL-MPs) on the scaffold physical properties and on the in vitro cell viability using a clonal human osteoblastic cell line (hFOB). Increasing the BL-MP content from 0% to 33.3% w/w showed a significant decrease in swelling degree (from 1245±56% to 570±35%). Scaffold pore size and distribution changed significantly as a function of BL-MP loading. Compressive modulus of scaffolds increased with increasing BL-MP amount up to 16.6% w/w (23.0±1.0kPa). No significant difference in cell viability was observed with increasing BL-MP loading. Based on these results, a content of 16.6% w/w MSIM particles was incorporated successfully in CH-G scaffolds, showing a controlled localised release of simvastatin able to influence the hFOB cell proliferation and the osteoblastic differentiation after 11 days.


Assuntos
Quitosana , Gelatina , Osteoblastos/metabolismo , Sinvastatina , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Linhagem Celular , Quitosana/química , Quitosana/farmacocinética , Quitosana/farmacologia , Gelatina/química , Gelatina/farmacocinética , Gelatina/farmacologia , Humanos , Teste de Materiais , Osteoblastos/citologia , Porosidade , Sinvastatina/química , Sinvastatina/farmacocinética , Sinvastatina/farmacologia
12.
Int J Mol Sci ; 16(9): 20492-510, 2015 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-26343649

RESUMO

Biodegradable poly(lactide-co-glycolide) (PLGA) nanoparticles, containing human parathyroid hormone (PTH (1-34)), prepared by a modified double emulsion-solvent diffusion-evaporation method, were incorporated in porous freeze-dried chitosan-gelatin (CH-G) scaffolds. The PTH-loaded nanoparticles (NPTH) were characterised in terms of morphology, size, protein loading, release kinetics and in vitro assessment of biological activity of released PTH and cytocompatibility studies against clonal human osteoblast (hFOB) cells. Structural integrity of incorporated and released PTH from nanoparticles was found to be intact by using Tris-tricine SDS-PAGE. In vitro PTH release kinetics from PLGA nanoparticles were characterised by a burst release followed by a slow release phase for 3-4 weeks. The released PTH was biologically active as evidenced by the stimulated release of cyclic AMP from hFOB cells as well as increased mineralisation studies. in vitro and cell studies demonstrated that the PTH bioactivity was maintained during the fabrication of PLGA nanoparticles and upon release. Finally, a content of 33.3% w/w NPTHs was incorporated in CH-G scaffolds, showing an intermittent release during the first 10 days and, followed by a controlled release over 28 days of observation time. The increased expression of Alkaline Phosphatase levels on hFOB cells further confirmed the activity of intermittently released PTH from scaffolds.


Assuntos
Regeneração Óssea , Ácido Láctico/química , Nanopartículas/química , Hormônio Paratireóideo/administração & dosagem , Ácido Poliglicólico/química , Alicerces Teciduais/química , Calcificação Fisiológica/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quitosana/química , Liberação Controlada de Fármacos , Gelatina/química , Humanos , Nanopartículas/ultraestrutura , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteoblastos/metabolismo , Hormônio Paratireóideo/farmacocinética , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Porosidade
13.
J Pharm Pharmacol ; 67(4): 525-36, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25515568

RESUMO

OBJECTIVES: The potential of poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) surface modified with octa-arginine (R8) for central nervous system (CNS) delivery was investigated. METHODS: PLGA NPs containing coumarin-6 or loperamide were surface modified using R8 and characterised for size, zeta potential, drug loading and release. We examined the cellular uptake of NPs in Madin-Darby Canine Kidney (MDCK) cells and CNS delivery of loperamide in a mouse model following intranasal (i.n.) and intravenous (i.v.) administration. KEY FINDINGS: NPs were 300-350 nm in diameter and of negative zeta potential which neutralised on R8 conjugation. Cellular uptake of R8-PLGA NPs was rapid compared with PLGA NPs and correlated with a high antinociceptive effect in mice by both the i.n. and i.v. routes. Little antinociceptive effect for PLGA NPs was observed reflecting their slow uptake in the in-vitro cell model. CONCLUSION: This study demonstrates the potential of R8-PLGA NPs as carriers of therapeutic agents to the CNS.


Assuntos
Arginina/química , Sistema Nervoso Central , Ácido Láctico/química , Loperamida/administração & dosagem , Nanoconjugados/química , Nanopartículas/química , Ácido Poliglicólico/química , Administração Intranasal , Administração Intravenosa , Analgésicos/administração & dosagem , Analgésicos/farmacologia , Animais , Linhagem Celular , Cumarínicos/administração & dosagem , Cães , Sistemas de Liberação de Medicamentos , Feminino , Loperamida/farmacologia , Masculino , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Poliésteres , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Polímeros/química , Tiazóis/administração & dosagem
14.
Pharm Dev Technol ; 20(4): 394-400, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24397821

RESUMO

The objective of the present study was to evaluate the influence of Prosolv® and Prosolv®: Mannitol 200 direct compression (DC) fillers on the physicomechanical characteristics of oral dispersible tablets (ODTs) of crystalline atorvastatin calcium. ODTs were formulated by DC and were analyzed for weight uniformity, hardness, friability, drug content, disintegration and dissolution. Three disintegration time (DT) test methods; European Pharmacopoeia (EP) method for conventional tablets (Method 1), a modification of this method (Method 2) and the EP method for oral lyophilisates (Method 3) were compared as part of this study. All ODTs showed low weight variation of <2.5%. Prosolv® only ODTs showed the highest tablet hardness of ∼ 73 N, hardness decreased with increasing mannitol content. Friability of all formulations was <1% although friability of Prosolv®:Mannitol ODTs was higher than for pure Prosolv®. DT of all ODTs was <30 s. Method 2 showed the fastest DT. Method 3 was non-discriminatory giving a DT of 13-15 s for all formulations. Atorvastatin dissolution from all ODTs was >60% within 5 min despite the drug being crystalline. Prosolv® and Prosolv®:Mannitol-based ODTs are suitable for ODT formulations by DC to give ODTs with high mechanical strength, rapid disintegration and dissolution.


Assuntos
Anticolesterolemiantes/química , Atorvastatina/química , Excipientes/química , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Manitol/química , Administração Oral , Anticolesterolemiantes/administração & dosagem , Atorvastatina/administração & dosagem , Cristalização , Composição de Medicamentos , Dureza , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Solubilidade , Comprimidos
15.
Arch Pharm Res ; 38(4): 566-73, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24170510

RESUMO

The aim of this study was to evaluate a novel 3-fluid concentric nozzle (3-N) spray drying process for the microencapsulation of omeprazole sodium (OME) using Eudragit L100 (EL100). Feed solutions containing OME and/or EL100 in ethanol were assessed visually for OME stability. Addition of OME solution to EL100 solution resulted in precipitation of OME followed by degradation of OME reflected by a colour change from colourless to purple and brown. This was related to the low pH of 2.8 of the EL100 solution at which OME is unstable. Precipitation and progressive discoloration of the 2-fluid nozzle (2-N) feed solution was observed over the spray drying time course. In contrast, 3-N solutions of EL100 or OME in ethanol were stable over the spray drying period. Microparticles prepared using either nozzle showed similar characteristics and outer morphology however the internal morphology was different. DSC showed a homogenous matrix of drug and polymer for 2-N microparticles while 3-N microparticles had defined drug and polymer regions distributed as core and coat. The results of this study demonstrate that the novel 3-N spray drying process can allow the microencapsulation of a drug using an incompatible polymer and maintain the drug and polymer in separate regions of the microparticles.


Assuntos
Química Farmacêutica/métodos , Composição de Medicamentos/métodos , Microesferas , Preparações Farmacêuticas/síntese química , Soluções Farmacêuticas/síntese química , Polímeros/síntese química , Soluções Farmacêuticas/uso terapêutico , Polímeros/uso terapêutico
16.
Int J Pharm Investig ; 4(2): 51-9, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25006549

RESUMO

AIM: Spray dried solid dispersion (SDP) of crystalline simvastatin (SIM) in a fast disintegrating matrix of superdisintegrants was studied as a method to enhance SIM dispersibility, rheology, compactibility and compressibility for incorporation into orodispersible tablets (ODTs). MATERIALS AND METHODS: The superdisintegrants investigated were crospovidone (CP), sodium starch glycollate (SSG) and calcium silicate (CS) were spray dried with simvastatin to form SDPs. RESULTS: The SDPs were characterized and the median particle size of SDPs was similar or greater than the SIM, contributing to good rheology of SDPs, while the low bulk density of SDPs indicated a high compactibility. Interestingly electron micrographs for SDPs showed a CP or CS carrier coating of the SIM crystals, contributing to its rheology. Thermal analysis and X-ray diffraction confirmed that SIM was crystalline in the SDPs and no interaction between SIM and any of the carrier(s) was shown by Fourier transform-infra red. Drug content analysis showed a SIM content of 90-95% in SDPs containing CP or CS, while a higher SIM content of 143% was found in SDP containing SSG. When formulated as ODTs, blend containing SIM SDPs in CP showed ease of tableting, regardless of the turret speed. In comparison, tablet blend consisting of a physical mix (PM) of SIM and CP could only be tableted at the lower turret speed of 7 rpm. ODTs formulated using SIM SDPs in CP showed a higher extent of dissolution, compared to the ODTs containing corresponding PM or the commercially available SIM Zocor(®) tablets (ANOVA, P < 0.05). CONCLUSION: SDP using disintegrants as carriers may offer an alternative formulation approach for ODTs of poorly soluble drugs.

17.
J Pharm Pharmacol ; 65(10): 1473-81, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24028614

RESUMO

OBJECTIVES: In this study, we examined the relative cellular uptake of nanoparticles (NPs) formulated using poly(lactic-co-glycolic acid) (PLGA) polymers with increasing degree of pegylation (PLGA-PEG) and their potential to deliver loperamide to the brain of a mouse. METHOD: NPs containing coumarin-6 or loperamide HCl were formulated using PLGA and PLGA-PEG, with PEG content of 5-15%, by the solvent evaporation method. NPs were characterised for size, surface charge, morphology, encapsulation efficiency and drug release. Cellular uptake of coumarin-6 NPs was examined in Caco-2 monolayers using confocal microscopy and central nervous system (CNS) delivery of loperamide HCl from the NPs was examined following intranasal administration in a mouse model. KEY FINDINGS: No difference in NP characteristics was observed, irrespective of degree of pegylation, except for the surface charge which increased with increasing PEG content. PLGA-PEG NPs were found to have increased cellular uptake in comparison to PLGA NPs. Interestingly, this pattern was reflected in the CNS delivery of loperamide HCl in the mouse model. CONCLUSION: The results from this study show that PLGA-PEG NPs have the potential to act as carriers for the noninvasive administration of therapeutic agents to the brain and possibly across other physiological barriers.


Assuntos
Encéfalo/metabolismo , Portadores de Fármacos/química , Ácido Láctico/química , Loperamida/administração & dosagem , Nanopartículas/química , Ácido Poliglicólico/química , Administração Intranasal , Animais , Células CACO-2 , Sobrevivência Celular/efeitos dos fármacos , Composição de Medicamentos , Endocitose , Humanos , Loperamida/farmacocinética , Camundongos , Camundongos Endogâmicos C57BL , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Propriedades de Superfície
18.
Curr Pharm Biotechnol ; 14(2): 220-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23360264

RESUMO

A major limitation of biological therapeutics is their propensity for degradation particularly in aqueous solutions hence resulting in their short shelf-life. In this study, the stability of trastuzumab (Herceptin®) intravenous (i.v.) solutions, an IgG1 monoclonal antibody (mAb), indicated for the treatment of HER2 positive breast cancer, stored under refrigerated conditions, was evaluated over 28 days. No change in visual appearance or average particle size was observed. The pH values of the trastuzumab i.v. solutions remained stable over time. Interestingly, no change in trastuzumab monomer concentration was observed throughout the 28-day study, as determined by SEC-HPLC. SDSPAGE showed only a monomer band corresponding to the molecular weight of trastuzumab. Circular dichroism spectra obtained following 28-day storage demonstrated integrity of the secondary structural conformation of trastuzumab. Results from this study show that trastuzumab i.v. solutions remain physically and structurally stable on storage at 2-8°C for 28 days. These findings suggest that trastuzumab in solution may not be as sensitive to degradation as expected for a mAb and therefore may have important implications in extending trastuzumab shelf life for clinical use and reducing associated healthcare cost.


Assuntos
Anticorpos Monoclonais Humanizados/química , Administração Intravenosa , Cromatografia Líquida de Alta Pressão/métodos , Dicroísmo Circular , Estabilidade de Medicamentos , Eletroforese em Gel de Poliacrilamida , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Soluções , Estresse Mecânico , Temperatura , Fatores de Tempo , Trastuzumab
19.
Clin Ther ; 34(11): 2221-9, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23149007

RESUMO

BACKGROUND: Administration of medications to pediatric patients is challenging because many drugs are not commercially available in appropriate dosage formulations and/or strengths. Consequently, these drugs are prepared extemporaneously as oral liquid (OL) formulations using marketed tablets or capsules. In many cases, the stability of these extemporaneous preparations, which may affect their tolerability, has not been documented. An alternative extemporaneous solid formulation, such as a fast-dispersing tablet (FDT), may offer enhanced stability as well as dosing flexibility because it may be administered as an orodispersible tablet or as a reconstituted suspension/solution. Although FDTs are available increasingly as patient-friendly oral dosage formulations, and their simple method of manufacture can be applied to extemporaneous formulations, such applications have not been explored to date. OBJECTIVES: The use of extemporaneous captopril OL formulations in hospitals in Ireland was surveyed, and the stability of the most commonly used captopril formulation (reference) was investigated and compared with that of a newly available extemporaneous FDT formulation. METHODS: The survey was carried out in 120 hospitals in the Republic of Ireland. The 56-day stability of the most commonly used formulation was compared with that of a newly available extemporaneous captopril FDT preparation. The captopril content of the formulations was measured by high-performance liquid chromatography analysis. Formulations were also monitored for changes in appearance, including color; odor; and pH (OLs only). RESULTS: The survey showed that extemporaneously prepared captopril OLs were extensively used, particularly in specialist children's hospitals. The most commonly used preparation was a xanthan gum-based oral suspension. Analysis of these OL preparations showed the OLs to have been stable up to day 7, but that the captopril concentration decreased to 72% to 84% at day 14 and to 59% to 68% at day 56; this decrease was accompanied by a pungent odor suggestive of captopril oxidation. In contrast, FDT formulations demonstrated greater stability, with 96% of captopril present at day 56. CONCLUSIONS: The results of this study support only a 7-day stability for the currently dispensed captopril OL in hospitals in Ireland. In contrast, a stability of at least 56 days was shown with the FDTs. The FDTs may represent an alternative and convenient oral solid extemporaneous preparation of captopril and, potentially, other extemporaneous pediatric medications.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Captopril/química , Serviço de Farmácia Hospitalar , Padrões de Prática Médica , Administração Oral , Inibidores da Enzima Conversora de Angiotensina/administração & dosagem , Captopril/administração & dosagem , Química Farmacêutica , Cromatografia Líquida de Alta Pressão , Cor , Composição de Medicamentos , Estabilidade de Medicamentos , Uso de Medicamentos , Dureza , Pesquisas sobre Atenção à Saúde , Humanos , Concentração de Íons de Hidrogênio , Irlanda , Oxirredução , Serviço de Farmácia Hospitalar/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Comprimidos , Tecnologia Farmacêutica/métodos , Fatores de Tempo
20.
Expert Opin Drug Deliv ; 9(12): 1463-74, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23061546

RESUMO

OBJECTIVE: To examine the potential of a novel 3-fluid nozzle spray drying technology to formulate differentiated layered microparticles (MPs) of diclofenac sodium (DFS)/ethyl cellulose (EC). METHODS: DFS/EC MPs were formulated using the inner and/or outer nozzles of a novel 3-fluid nozzle and compared with MPs formed using conventional (2-fluid) spray drying. MPs were characterised for particle size and for morphology by TEM and SEM. Distribution of DFS and EC of MPs was analysed by FT-IR and DSC. A two-factor, three-level (3(2)) factorial design was applied to investigate the effect and interaction of total feed solid content (TSC) and feed flow rate (FFR) on MP size, D(50%) and D(90%), bulk density and MP yield. RESULTS: Interestingly, TEM demonstrated that MPs formed by 3-fluid nozzle spray drying showed a heterogeneous internal morphology consisting of a core and coat, characteristic of a microcapsule. In comparison, MPs from conventional spray drying showed a homogeneous internal morphology, characteristics of a matrix system. This differential distribution of DFS/EC was supported by FT-IR and DSC. Results of multiple linear regression analysis showed a linear relationship for the effect of TSC and FFR on all responses except for D(50%) where a quadratric model was valid. The effect of TSC/FFR on MP size and yield was similar to conventional spray drying. CONCLUSION: The novel 3-fluid nozzle spray drying offers a new method of designing layered microparticles or microcapsules which can have wide applications from drug stabilisation to controlled drug delivery and targeting.


Assuntos
Celulose/análogos & derivados , Inibidores de Ciclo-Oxigenase/química , Diclofenaco/química , Tecnologia Farmacêutica/métodos , Aerossóis , Varredura Diferencial de Calorimetria , Celulose/química , Química Farmacêutica/métodos , Portadores de Fármacos , Microscopia Eletrônica , Microesferas , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Tecnologia Farmacêutica/instrumentação
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