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1.
Mater Sci Eng C Mater Biol Appl ; 129: 110211, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34579874

RESUMO

In part 1, we have investigated drug release by solid-solution single fibers comprising a sparingly water-soluble drug (ibuprofen) and a highly water-soluble dual excipient (low-molecular-weight hydroxypropyl methyl cellulose (HPMC) and polyoxyl stearate (POS)). In this part, fibrous dosage forms of the same formulation are prepared by 3D-micro-patterning, tested, and modeled. Upon immersion in a small volume of dissolution fluid, the dosage forms rapidly swelled and formed a low-viscosity medium, which subsequently dissolved. The dissolution time increased slightly with volume fraction of the fibers, φs, in the solid dosage form, but was less than 25 minutes even up to φs = 0.65. After dosage form dissolution, the fluid was supersaturated by a factor of two; the drug concentration then gradually decreased to solubility. The solubility was proportional to the concentration of POS, and was enhanced by a factor of six at φs = 0.65 (the most densely-packed dosage form). Theoretical models suggest that the dissolution fluid percolates the contiguous void space almost immediately, and the HPMC-POS fibers expand isotropically as water diffuses in. Because the void space remains contiguous in isotropic expansion, the dissolution fluid continues to percolate through and diffuse into the fibers. Thus, even the densely-packed dosage forms form a low-viscosity medium that deforms and dissolves rapidly. Consequently, the solid-solution fibrous dosage forms enable enhanced release rate, supersaturation, and solubility of sparingly-soluble drugs.


Assuntos
Preparações Farmacêuticas , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes , Derivados da Hipromelose , Solubilidade
2.
Int J Pharm ; 605: 120834, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34192587

RESUMO

A non-destructive discrimination method for crystals in solid dosage drug forms was first developed using a combination of Raman spectroscopy and X-ray micro-computed tomography (X-ray CT). Identification of the crystal form of an active pharmaceutical ingredient (API) at the appropriate pharmaceutical dosage is crucial, as the crystal form is a determinant of the quality and performance of the final formulation. To develop a non-destructive analytical methodology for the discrimination of solid API crystals in a solid dosage form, we utilized a combination of Raman spectroscopy and X-ray CT to differentiate between ranitidine crystal polymorphs (forms 1 and 2) in tablet formulations containing three excipients. The difference in electron density correlated with the true density between ranitidine polymorphs, thereby enabling the discrimination of crystal forms and visualization of their three-dimensional spatial localization inside the tablets through X-ray CT imaging. Furthermore, X-ray CT imaging revealed that the crystal particles were of varying densities, sizes, and shapes within the same batch. These findings suggest that X-ray CT is not only an imaging tool but also a unique method for quantitative physicochemical characterization to study crystal polymorphs and solid dosage forms.


Assuntos
Ranitidina , Análise Espectral Raman , Cristalização , Formas de Dosagem , Comprimidos , Microtomografia por Raio-X
3.
Anal Chem ; 93(25): 8986-8993, 2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34142802

RESUMO

A new combinatory Raman subtechnique of low-frequency and micro-spatially offset Raman spectroscopy (denoted micro-SOLFRS) is demonstrated via analysis of pharmaceutical solid dosage forms. A variety of different (multilayer/multicomponent) model systems comprising celecoxib, α-lactose (the anhydrous and monohydrate form), and polyvinylpyrrolidone (PVP) were probed to test the potency of this newly developed technique to, for example, provide qualitative and quantitative information on surface and subsurface layer characteristics, including their thicknesses as well as enable monitoring of surface-driven solid-state form transformations. A simultaneous collection of low- and, the more commonly used, mid-frequency data enabled a direct comparison between these spectral regions, where the low-frequency domain (hence, micro-SOLFRS) proved superior for every respective analysis carried out herein.


Assuntos
Preparações Farmacêuticas , Análise Espectral Raman , Diagnóstico por Imagem , Formas de Dosagem , Lactose , Povidona
4.
AAPS PharmSciTech ; 22(5): 187, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-34155595

RESUMO

Several drugs have poor oral bioavailability due to low or incomplete absorption which is affected by various effects as pH, motility of GI, and enzyme activity. The gastroretentive drug delivery systems are able to deal with these problems by prolonging the gastric residence time, while increasing the therapeutic efficacy of drugs. Previously, we developed a novel technology to foam hot and molten dispersions on atmospheric pressure by a batch-type in-house apparatus. Our aim was to upgrade this technology by a new continuous lab-scale apparatus and confirm that our formulations are gastroretentive. At first, we designed and built the apparatus and continuous production was optimized using a Box-Behnken experimental design. Then, we formulated barium sulfate-loaded samples with the optimal production parameters, which was suitable for in vivo imaging analysis. In vitro study proved the low density, namely 507 mg/cm3, and the microCT record showed high porosity with 40 µm average size of bubbles in the molten suspension. The BaSO4-loaded samples showed hard structure at room temperature and during the wetting test, the complete wetting was detected after 120 min. During the in vivo study, the X-ray taken showed the retention of the formulation in the rat stomach after 2 h. We can conclude that with our device low-density floating formulations were prepared with prolonged gastric residence time. This study provides a promising platform for marketed active ingredients with low bioavailability.


Assuntos
Sulfato de Bário/síntese química , Sulfato de Bário/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Absorção Gastrointestinal/efeitos dos fármacos , Animais , Sulfato de Bário/administração & dosagem , Disponibilidade Biológica , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/síntese química , Preparações de Ação Retardada/farmacocinética , Formas de Dosagem , Mucosa Gástrica/efeitos dos fármacos , Mucosa Gástrica/metabolismo , Absorção Gastrointestinal/fisiologia , Masculino , Porosidade , Ratos , Ratos Endogâmicos F344
5.
Nutrients ; 13(5)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069842

RESUMO

Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aß-amyloid (Aß) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(-)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of ß-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (ScEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aß plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.


Assuntos
Aldeídos/administração & dosagem , Doença de Alzheimer/tratamento farmacológico , Monoterpenos Ciclopentânicos/administração & dosagem , Suplementos Nutricionais , Azeite de Oliva/administração & dosagem , Fenóis/administração & dosagem , Placa Amiloide/tratamento farmacológico , Doença de Alzheimer/patologia , Peptídeos beta-Amiloides/metabolismo , Animais , Encéfalo/patologia , Modelos Animais de Doenças , Formas de Dosagem , Feminino , Camundongos , Camundongos Transgênicos , Placa Amiloide/patologia , Pós , Espectroscopia de Infravermelho com Transformada de Fourier
6.
Clin Pharmacol Ther ; 110(4): 1127-1135, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34110632

RESUMO

Public knowledge-based application ("Kouchi-shinsei" in Japanese) is unique to Japan, implemented to eliminate the off-label use of unapproved indications, dosages, and administrations because of drug lag. The guidance for public knowledge-based application was issued in 1999. This study comprehensively investigated the trends of items approved by public knowledge-based application in Japan during the last 2 decades. Prescription drugs approved from January 2000 to December 2019 were surveyed. In Japan, 1,855 drugs were approved within the target survey period. Among them, 219 (11.8%) were approved by public knowledge-based application. Considering the changes in the number of items approved by public knowledge-based application over the years, the number of items approved in 2000 was 7, reaching a maximum of 34 items in 2011, and decreased after that, 8 items were approved in 2019. The regulatory characteristics of drugs approved by public knowledge-based application and those of other drugs were compared. By public knowledge-based application, more anticancer and pediatric drugs were approved (P < 0.001), and only one drug for orphan diseases was approved (P < 0.001). In addition, the review time of public knowledge-based applications was significantly shorter than that of normal applications regardless of time point. The approval system using public knowledge-based application began in 2000, following issuance of the "Guidance for off-label use of prescription drugs." Furthermore, the approved items were mostly drugs for cancer, infectious diseases, and pediatric drugs. We anticipate the promotion of public knowledge-based application to accommodate the approval of drugs for orphan diseases.


Assuntos
Aprovação de Drogas/legislação & jurisprudência , Uso Off-Label/legislação & jurisprudência , Medicamentos sob Prescrição , Anti-Infecciosos , Antineoplásicos , Fármacos Cardiovasculares , Fármacos do Sistema Nervoso Central , Ensaios Clínicos como Assunto , Formas de Dosagem , Fármacos Gastrointestinais , Humanos , Japão , Bases de Conhecimento , Compostos Radiofarmacêuticos , Agentes Urológicos , Vacinas
7.
Diabetes Res Clin Pract ; 176: 108857, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33965450

RESUMO

The history of insulin is rightly considered one of the most beautiful stories in medicine which goes even further than the extraordinary result of tens of millions of lives saved. Without a doubt, it constitutes a major achievement for medical science which, especially in the last 50 years, has led to an impressive acceleration in the succession of new treatment opportunities. We are going to describe the history of insulin therapy, the history we lived from two different angles as people living with type 1 diabetes, and obviously also as diabetologists, but as diabetologists with diabetes. Without a doubt, insulin and his story constitutes a major achievement for medical science which has led to an impressive acceleration in the succession of new treatment opportunities. Care opportunities that have not only allowed fundamental improvements in outcomes, but have also and above all impacted the quality of life of people with diabetes. Summarizing one hundred years of insulin is no simple endeavor. In our view, it would be easier, and probably more befitting, to focus on the last 50 years, namely the period we have lived closely and personally together with insulin. More to the point, these last 50 years have witnessed a dramatic acceleration of research and innovation. In our opinion, it is precisely the innovations in insulin therapy introduced from the last decades that fully justify the description of events in this incredible period as "the miracle of insulin". We'll describe how the most important innovations introduced in the last decades had impact on what we have nowadays, as patients and diabetologits: today, we can finally adapt insulin therapy to the patient's life or lifestyle, reversing what was the perception of patients until 20 years, when insulin was considered, by the most, as an obstacle, which seemed insurmountable to some, to a free and unconstrained life.


Assuntos
Diabetes Mellitus Tipo 1/história , Endocrinologistas/história , Insulina/história , Atividades Cotidianas , Pesquisa Biomédica/história , Pesquisa Biomédica/tendências , Diabetes Mellitus Tipo 1/tratamento farmacológico , Formas de Dosagem , Sistemas de Liberação de Medicamentos/história , Sistemas de Liberação de Medicamentos/instrumentação , Sistemas de Liberação de Medicamentos/métodos , Sistemas de Liberação de Medicamentos/tendências , Descoberta de Drogas/história , Descoberta de Drogas/tendências , Endocrinologia/história , Endocrinologia/instrumentação , Endocrinologia/tendências , História do Século XX , História do Século XXI , Humanos , Insulina/administração & dosagem , Insulina/química , Médicos/história , Qualidade de Vida
8.
Int J Pharm ; 603: 120702, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33989752

RESUMO

In this work, the versatility of pressure extrusion-based printing (PEBP) was used as 3D printing process to create long-acting implantable dosage forms. Different release profiles were achieved based on the drug concentration, the way of preparation and the design of the final implants. Polycaprolactone (PCL) was used as the polymer to sustain the release of the loaded drug. Paliperidone palmitate (PP), a BCS Class II drug, used in the treatment of schizophrenia, was used as the model drug. Two PP concentrations (e.g. 5 and 10% w/w) as well as two methods of preparation before the 3D printing process, mortar and pestle and cryogenic milling, were evaluated. The amorphous state of PP was obtained by using cryogenic milling and it was maintained after printing. Two designs were printed by PEBP, a ring and a disk, to evaluate their impact on the release profile of PP. During the in vitro dissolution tests, the implant design, the amount of PP, as well as the crystalline or amorphous state of PP have shown to influence the drug release profile. During the successive steps of preparation of the long-acting implants, blends and raw materials were characterized by DSC and XRD.


Assuntos
Palmitato de Paliperidona , Impressão Tridimensional , Formas de Dosagem , Liberação Controlada de Fármacos , Polímeros
9.
AAPS PharmSciTech ; 22(4): 142, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33893566

RESUMO

Apremilast (APST) is an effective inhibitor of phosphodieasterase 4 (PDE4) which is the first oral drug for the treatment of adult patients with active psoriatic arthritis. However, Apremilast's low solubility restricts its dissolution and bioavailability. In this study, APST solid dispersion with D-α-tocopherol polyethylene glycol 1000 succinate (TPGS) and Poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) was developed to improve the dissolution and bioavailability of APST by spray drying. A series of TPGS were synthesized to elucidate the effect of the ratio of monoester to diester on solubilizing capacity. X-ray powder diffraction (XRPD), differential scanning calorimetry (DSC), and Fourier transform infrared spectrophotometry (FT-IR) were used to characterize the solid dispersion, and the results showed that APST was amorphous in solid dispersion. In vitro dissolution study showed that the dissolution rate of solid dispersion in phosphate buffered saline (pH 6.8) was remarkably increased, reaching a release of 90% within 10 min. Moreover, in vivo pharmacokinetics study revealed that the bioavailability of solid dispersion in rats had significant improvement. In particular, its Cmax and AUClast were nearly 22- and 12.9-fold greater as compared to APST form B, respectively. In conclusion, APST solid dispersion with TPGS and PVPVA is an alternative drug delivery system to improve the solubility and oral bioavailability of APST.


Assuntos
Formas de Dosagem , Inibidores da Fosfodiesterase 4/química , Povidona/análogos & derivados , Talidomida/análogos & derivados , Vitamina E/química , Animais , Disponibilidade Biológica , Varredura Diferencial de Calorimetria , Inibidores da Fosfodiesterase 4/farmacocinética , Povidona/química , Difração de Pó , Ratos , Solubilidade , Espectroscopia de Infravermelho com Transformada de Fourier , Talidomida/química , Talidomida/farmacocinética
10.
J AOAC Int ; 104(2): 355-367, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-33871029

RESUMO

BACKGROUND: According to literature reports, none of the previous methods of analysis had touched the multivariate approach for the quantification of significant factors affecting the interaction of dobutamine or hexoprenaline with Terbium. OBJECTIVE: Two novel ß-adrenergic agonists-lanthanide chemosensors were prepared for the determination of dobutamine and hexoprenaline in their pure and pharmaceutical dosage forms and in urine samples. Fabrication of the two chemosensors was based on their ligand-metal interaction with the lanthanide Terbium. METHODS: A Plackett-Burman Design (PBD) was selected for the screening of four main variables (reaction time, metal volume, pH, and temperature). Applying Response Surface Methodology (RSM), a Central Composite Design (CCD) was executed for the optimization of the significant factors with narrower upper and lower limits. Spectrophotometric technique was exploited for the analysis of the two chemosensors. RESULTS: Maximum absorption was obtained at 299 and 298 nm for dobutamine-terbium and hexoprenaline-terbium complexes, respectively. Only factors that were found to bear significant effects on the formed complexes were promoted to the optimization level. Model verification was carried out, where target results coincided with those at the predicted levels, indicating the efficiency of the two proposed models. Validation of the proposed was implemented and linear ranges were found to be 3.30-13.50 and 1.90-10.00 µg/mL, for dobutamine and hexoprenaline, respectively. CONCLUSIONS: Recovery and relative standard deviation values by application in pure powder, pharmaceutical dosage forms and spiked urine samples indicated high accuracy and reproducibility. Wide-ranging linear values and comparatively low detection limits inferred the effectiveness of the proposed method. HIGHLIGHTS: RSM for optimization of spectrophotometric determination of dobutamine and hexoprenaline ß-adrenergic agonists-lanthanide chemosensors; PBD was used for screening and CCD for optimization of variables affecting the spectrophotometric method; Determination of dobutamine and hexoprenaline in pure powder, pharmaceutical dosage form, and spiked urine samples was accomplished after method validation.


Assuntos
Preparações Farmacêuticas , Térbio , Agonistas Adrenérgicos beta , Formas de Dosagem , Reprodutibilidade dos Testes , Espectrofotometria
11.
AAPS PharmSciTech ; 22(4): 141, 2021 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-33884533

RESUMO

The taste of drug substances plays a key role in the development of paediatric formulations with suitable organoleptic properties. The aim of the study was to evaluate the taste masking effectiveness of Smartseal 30D and ReadyMix on a range of bitter drug substances such as diphenhydramine HCl (DPD), ibuprofen lysine (IBU-LS), and phenylephrine HCl (PPH) for the development of paediatric dosage forms. The drugs were microencapsulated in the polymer carriers at 10-20% loadings using spray-drying processing. Spray drying of drug formulations was optimized in terms of percent yield and encapsulation efficiency followed by physicochemical characterization in order to identify the drugs' physical state in the polymer microparticles. The in vivo taste masking efficiency was evaluated using human test panel and showed noticeable reduction of drug's bitterness at all loadings in comparison to the bulk substances.


Assuntos
Formas de Dosagem , Composição de Medicamentos , Paladar , Administração Oral , Criança , Humanos , Ibuprofeno/análogos & derivados , Ibuprofeno/farmacologia , Lisina/análogos & derivados , Lisina/farmacologia , Preparações Farmacêuticas , Polímeros , Solubilidade
12.
Luminescence ; 36(7): 1572-1583, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33864352

RESUMO

Approved, basic, effective and successful spectroscopic strategies (spectrophotometric and spectrofluorimetric) were created to measure seven cephalosporins: cefpiramide (I), cefuroxime (II), cefoxitin (III), ceftazidime (IV), cefpirome (V), ceftobiprole (VI), and ceftriaxone (VII). These strategies used a two-fold complex arrangement response for the drug amino groups with Eosin Y (EY). The examined drugs were determined spectrophotometrically at 542-550 nm in acetic acid derivative buffer. The examined drugs were determined spectrofluorimetrically by measuring their quenching effect on EY local fluorescence at 545 nm after excitation at 305 nm. The absorbance-intensity plots were rectilinear over the ranges 20-100, 10-130, 20-220, 30-230, 10-210, 20-180 and 10-130 µg ml-1 for I, II, III, IV, V, VI, and VII samples, respectively. The fluorescence-intensity plots were rectilinear over the ranges 0.5-1.5, 0.1-0.9, 0.3-1.5, 0.5-2.5, 0.1-0.9, 0.5-2.5 and 0.1-1.0 µg ml-1 for I, II, III, IV, V, VI, and VII samples, respectively. The recommended materials were certified as adhering to International Council for Harmonisation (ICH) guidelines and were used to examine the tested drugs in different dosage forms and in human plasma tests. The approved materials matched the reference materials.


Assuntos
Cefalosporinas , Preparações Farmacêuticas , Formas de Dosagem , Amarelo de Eosina-(YS) , Humanos , Espectrometria de Fluorescência , Espectrofotometria
13.
AAPS PharmSciTech ; 22(3): 85, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33650023

RESUMO

In this study, an attempt was made to produce Liqui-Tablets for the first time. This was carried out through the compaction of naproxen Liqui-Pellets. The incentive to convert the novel Liqui-Pellet into Liqui-Tablet was due to the array of inherent advantages of the popular and preferred tablet dosage form. The study showed that naproxen Liqui-Tablet could be successfully produced and the rapid drug release rate (100% drug release ~ 20 min) could be achieved under pH 1.2, where naproxen is insoluble. It was observed that the different pH of the dissolution medium affected the trend of drug release from formulations with varying amounts of liquid vehicle. The order of the fastest drug-releasing formulations was different depending on the pH used. The presence of Neusilin US2 showed considerable enhancement in the drug release rate as well as improving Liqui-Tablet robustness and hardness. Furthermore, images from X-ray micro-tomography displayed a uniform distribution of components in the Liqui-Tablet. The accelerated stability studies showed acceptable stability in terms of dissolution profile.


Assuntos
Composição de Medicamentos/métodos , Naproxeno/administração & dosagem , Naproxeno/síntese química , Tecnologia Farmacêutica/métodos , Administração Oral , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/síntese química , Anti-Inflamatórios não Esteroides/farmacocinética , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes/administração & dosagem , Excipientes/síntese química , Excipientes/farmacocinética , Naproxeno/farmacocinética , Comprimidos
14.
Int J Pharm ; 601: 120518, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33775729

RESUMO

A novel approach to solid dosage form design is investigated, whereby instead of blending the ingredients and subsequently compacting the mixture, the dosage form is made by assembling prefabricated components, each with a specific function. The approach was used to formulate a weak-base API (active pharmaceutical ingredient), such that the modular dosage forms exhibited pH-independent drug release. Tablet-like dosage forms of ciprofloxacin (CPR), used as model weak-base drug, were prepared in order to generate dosage forms exhibiting pH-independent drug release. The dosage forms were made by assembling two types of prefabricated modules onto 3D stacks. The modules were hydroxypropyl methylcellulose circular film wafers, loaded with either CPR or citric acid (CA). CA-wafers served the function of pH-modifier modules in the microenvironment of the dosage form during the dissolution process. In vitro drug release from dosage forms consisting of CA- and CPR-wafers stacked in alternate sequence was compared with the release from assemblies containing CPR-wafers only, under pH = 1.2 and pH = 6.8 conditions. In the absence of CA-wafers, CPR release was ~25-fold slower at pH = 6.8 compared to pH = 1.2. Inclusion of CA-wafers in the dosage form assembly accelerated and decelerated drug release at pH = 6.8 and pH = 1.2, respectively, which resulted in overlapping drug release profiles under the two pH conditions. The two drug release profiles met the criteria for sameness as assessed by the f1 (difference) and f2 (similarity) factors. Modeling of drug release kinetics pointed toward polymer erosion as the primary mechanism of drug release for the overlapping pH = 1.2 and pH = 6.8 profiles. In terms of their drug release properties, the multi-modular dosage form assemblies exhibited the attributes and behavior of single bodies, rather than the combined contributions from multiple individually-operating modules. The initial geometry of the dosage form, characterized by the surface area (SA), volume (V) and SA/V ratio accounted for drug release kinetics in the same fashion as for traditional tablet compacts.


Assuntos
Solubilidade , Preparações de Ação Retardada , Formas de Dosagem , Concentração de Íons de Hidrogênio , Derivados da Hipromelose , Comprimidos
15.
Artigo em Inglês | MEDLINE | ID: mdl-33740691

RESUMO

Lutetium-177 [177Lu] tetra-azacyclododecanetetra-acetic acid [DOTA]-(Tyr3)-octreotate [TATE] ([177Lu]Lu-DOTA-TATE) is a radiopeptide used for peptide receptor radionuclide therapy in patients with neuroendocrine tumours (NETs). This radiopeptide is made by labelling the ligand octreotate with Lutetium-177 using the linker DOTA. After labelling, and before clinical application quality control of the radiopeptide is needed and the radiochemical purity is assessed. Acceptance limits for radiochemical purity should be within 90-110% of the label claim for radiopharmaceuticals for diagnostic use and within 95-105% of the label claim for radiopharmaceuticals for therapeutic use. Moreover, the amount of unlabelled [177Lu]LuCl3 cannot exceed 2% of the radioactive dose. Since no monograph is available for [177Lu]Lu-DOTA-TATE in the European Pharmacopeia (Ph Eur), this article describes the development and validation of a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection and radiodetection. A Waters Acquity Arc UHPLC system equipped with a Waters 2998 photodiode array (PDA) detector was used coupled to a Berthold Lb 514 Flowstar detector equipped with a BGO-X gamma measuring cell. A reversed phase Symmetry Shield C18 column (4.6 mm × 250 mm, 5 µm) was used for chromatographic separation. A flow of 1.5 mL/min was maintained during analysis, using 0.1% TFA in water as mobile phase A and 0.1% TFA in ACN as mobile phase B. The retention time was around 1.7 min and 13.5 min for [177Lu]LuCl3 and [177Lu]Lu-HA-DOTA-TATE, respectively. Stock solutions of [177Lu]LuCl3 were made by serial dilution and were injected to test for linearity, accuracy and precision, carry over and signal-to-noise ratio. A [177Lu]Lu-HA-DOTA-TATE sample was prepared and injected to determine the carry over. The results showed that the method is linear over a range of 0.300-130 MBq/mL, which covers the range for clinical samples, provided that the clinical sample is diluted ten times before analysis. The LLOQ can be measured accurately even after dilution, with a signal-to-noise ratio of at least 5. In short, the method is accurate, precise and sensitive and can be implemented as part of the quality control of [177Lu]Lu-HA-DOTA-TATE.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Octreotida/análogos & derivados , Compostos Organometálicos , Compostos Radiofarmacêuticos , Formas de Dosagem , Modelos Lineares , Octreotida/análise , Octreotida/química , Compostos Organometálicos/análise , Compostos Organometálicos/química , Compostos Radiofarmacêuticos/análise , Compostos Radiofarmacêuticos/química , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
16.
AAPS PharmSciTech ; 22(3): 114, 2021 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-33763759

RESUMO

Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater Cmax than LSF, LSF-LA, and LSF-LA PLM. Designed facile LSF-LA PLM tablet dosage form has potential for an immediate decrease in the postprandial glucose levels in patients of T1D.


Assuntos
Diabetes Mellitus Tipo 1/metabolismo , Jejuno/metabolismo , Ácido Linoleico/farmacocinética , Nanopartículas/metabolismo , Pentoxifilina/análogos & derivados , Perfusão/métodos , Administração Oral , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Diabetes Mellitus Tipo 1/tratamento farmacológico , Formas de Dosagem , Jejuno/efeitos dos fármacos , Ácido Linoleico/administração & dosagem , Ácido Linoleico/síntese química , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Pentoxifilina/administração & dosagem , Pentoxifilina/síntese química , Pentoxifilina/farmacocinética , Ratos , Ratos Wistar , Comprimidos
17.
An. R. Acad. Nac. Farm. (Internet) ; 87(1): 105-108, ene.-mar. 2021.
Artigo em Espanhol | IBECS | ID: ibc-201636

RESUMO

Intento acercar la oficina de farmacia desde su legislación hasta su ejercicio profesional centrándonos en puntos menos conocido como la atención farmacéutica y calidad de vida el perfil psiquiátrico que acompaña a la no adherencia al tratamiento médico. Quisiera sacar la Conclusión de que he conseguido interesar para que se conozca la misión de los farmacéuticos y técnicos en farmacia que las integran


I try to bring the pharmacy office closer from its legislation to its professional practice, focusing on less known points such as pharmaceutical care and quality of life, the psychiatric profile that accompanies non-adherence to medical therapy. I would like to draw the conclusion that I have managed to interest so that the mission of the pharmacists and pharmacy technicians who are part of them is known


Assuntos
Humanos , Assistência Farmacêutica/legislação & jurisprudência , Formas de Dosagem , Comercialização de Produtos , Adesão à Medicação , Qualidade de Vida , Espanha , Satisfação do Paciente
18.
J Chromatogr Sci ; 59(7): 650-658, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33575745

RESUMO

Vancomycin and teicoplanin are glycopeptide antibacterials that inhibit the bacteria cell wall synthesis showing activity against gram-positive bacteria. Development of the sensitive method is of great importance for quality control of these drugs that are fermentation products. Modification of the fermentation conditions could cause the differences in the relative amount of the total substance or component, as it is the case with teicoplanin. The main objective of this study was development of the sensitive and effective ultra high performance liquid chromatography - tandem mass sprectrometry (UHPLC-MS/MS) method for simultaneous quantification of vancomycin, all six subcomponents of teicoplanin, and its pharmacopoeial impurity A in pharmaceutical forms. The scientific-based Quality by Design approach was implemented in the MS and UHPLC method development. Detection and quantification of analytes were carried out in positive electrospray ion mode by multiple reaction monitoring. Capillary voltage, cone voltage and collision energy were optimized by implementing experimental design methodology and optimal values for each fragment ion were obtained by performing experiments according to 'Rechtschaffen' design matrix. An ACQUITY CSH Phenyl-hexyl (2.1 × 50 mm, particle size 1.7 µm) column was chosen for the separation under the gradient elution mode with the mobile phase consisted of 0.1% formic acid in water (mobile phase A) and acetonitrile (mobile phase B). Optimal gradient elution parameters were achieved by applying 'Rechtschaffen' design too. Method operable design regions were constructed for investigated MS and chromatographic parameters. The method was fully validated, and its applicability was confirmed throughout the ability to follow the behavior of vancomycin and teicoplanin under stress conditions.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Glicopeptídeos/análise , Espectrometria de Massas em Tandem/métodos , Formas de Dosagem , Limite de Detecção , Modelos Lineares , Controle de Qualidade , Reprodutibilidade dos Testes
19.
Expert Opin Ther Pat ; 31(7): 663-686, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33605825

RESUMO

INTRODUCTION: The current availability of dosage forms designed specifically for children is limited, constituting common practice the use of unlicensed or off-labeled medicines and extemporaneous preparations. Swallowing difficulties and taste aversion are the primary reasons for medicine rejection; therefore, enhancing palatability and ease of administration are the most common approaches adopted to overcome these issues. AREAS COVERED: A search of patents was performed for pediatric dosage forms and devices. The review aims to provide an overview on new formulation approaches and technologies adopted to develop pediatric-friendly dosage forms and devices, as well as on the regulatory efforts aiming to support the pediatrics market. EXPERT OPINION: Children deserve medicines of the same efficacy, quality and safety as adults. The present review highlights the momentum developed by pharmaceutical industries in the field of pediatrics, since more than 60 patents have been published in the last 5 years. An increasing interest, especially in mini-tablets, orodispersible, and chewable dosage forms, as well as on excipients and methods, to achieve sufficient taste-masking was identified, recognizing also the need for coordinated research networks and sustainable collaborations across the public and private sectors to provide better medicines for children.


Assuntos
Química Farmacêutica/métodos , Formas de Dosagem , Tecnologia Farmacêutica/métodos , Administração Oral , Criança , Indústria Farmacêutica/métodos , Excipientes/química , Humanos , Patentes como Assunto , Preparações Farmacêuticas/administração & dosagem , Preparações Farmacêuticas/química , Paladar
20.
Mater Sci Eng C Mater Biol Appl ; 120: 110144, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33545806

RESUMO

Many drug therapies could be greatly improved by dosage forms that reside in the stomach for prolonged time and release the drug slowly. In this work, therefore, slow-release fibrous dosage forms that expand rapidly in the gastric fluid to prevent their passage into the intestines are investigated. The dosage forms consisted of acetaminophen drug and a high-molecular-weight hydroxypropyl methyl cellulose (HPMC) excipient. Upon immersion in a dissolution fluid, they transitioned to viscous, and expanded in proportion to the square-root of time and the reciprocal of fiber radius. The normalized axial expansion was up to 100 percent by fifteen minutes, fast enough to convert a swallowable, 10-mm diameter disk into a gastroretentive, 20-mm diameter viscous gel. The drug was released slowly, eighty percent in 2-8.4 hours. Theoretical models show that the fibrous dosage forms expand rapidly due to the fast diffusion of dissolution fluid into the thin fibers. The fibers then coalesce into a uniform viscous gel, and the diffusion length increases from the radius of the thin fibers to the half-thickness of the gelated dosage form. Consequently, drug diffusion out is slow, and the twin requirements, fast expansion and prolonged drug release, are simultaneously satisfied.


Assuntos
Sistemas de Liberação de Medicamentos , Preparações Farmacêuticas , Preparações de Ação Retardada , Formas de Dosagem , Liberação Controlada de Fármacos , Excipientes , Derivados da Hipromelose , Solubilidade , Comprimidos
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