RESUMO
BACKGROUND: Aphthous stomatitis is one of the most common oral mucosal diseases. Due to the commonness of recurrent aphthous stomatitis and considering the anti-inflammatory, analgesic, and tissue regenerative properties of atorvastatin and the lack of a study on the effect of statins on minor recurrent aphthous stomatitis, this study investigates the effect of atorvastatin mucoadhesive tablets as a topical treatment on reduction of symptoms and duration of this disease. METHODS: This study is a randomized, double-blinded clinical trial. Patients were divided into two groups, atorvastatin and, placebo; each of the patients received three mucoadhesive tablets daily in the morning, noon, and night. Finally, the patients were examined on days 0 (baseline), 3, 5, and 7 to determine the diameter of the inflammatory halo. The VAS scale was used to evaluate pain intensity for up to 7 days after each meal. The data was entered into SPSS 24 software and analyzed. RESULTS: The halo diameter did not significantly differ between the two groups on baseline (P > 0.05). However, on the study's third, fifth, and seventh days, the difference between the two groups was remarkable, so in the atorvastatin group, the size of the lesions decreased in shorter healing time (P < 0.05). In addition, the patient's pain intensity (VAS) also showed a significant decrease in the atorvastatin group except on the first, second, and seventh days of the study (P < 0.05). CONCLUSION: Atorvastatin mucoadhesive tablets effectively reduce the pain of patients with minor recurrent aphthous stomatitis and reduce the size and healing time of the lesions, so their application should be considered in treating minor recurrent aphthous stomatitis. The present study was approved by the Medical Ethics Committee of Mazandaran University of Medical Sciences with the ethics code IR.MAZUMS.REC.1400.8346. Also, this study received code IRCT20170430033722N4.
Assuntos
Estomatite Aftosa , Humanos , Estomatite Aftosa/tratamento farmacológico , Atorvastatina/uso terapêutico , Resultado do Tratamento , Método Duplo-Cego , Comprimidos/uso terapêuticoRESUMO
The development of a raw material into an acceptable pharmaceutical excipient involves evaluation of the physicochemical and formulation properties of the potential raw material. Results from these evaluations may serve as a guide to subsequent use of the substance. The objective of the study was to evaluate the physicochemical and microbiological properties of the stem bark gum of Cordia millenii tree in conventional release paracetamol tablets. From the physicochemical evaluations, the gum was slightly acidic and soluble in all the aqueous-based solvents, except 0.1 N HCl in which it was sparingly soluble. All the absorptive properties of the gum indicated tablet disintegrating potential for tablet formulation. The total ash of the gum was higher than that of the international standard gum arabic. Micromeritic properties of the gum indicated the need for a flow aid to improve its flowability. There were no harmful microorganisms detected in the gum. Aerobic organisms and moulds and yeast were detected within permissible limits. Tablets formulated using six different concentrations of gum dispersions as a binder were generally soft and failed the USP T80 standard of dissolution, indicating poor binding and drug releasing properties. Quality control properties of three different batches of tablets containing varying concentrations of the dry gum as a disintegrating agent were comparable to tablets containing equal concentrations of corn starch. The in vitro drug releases were similar at all-time points of drug evaluation. The gum can therefore be considered as a good disintegrant in the formulation of conventional release tablets.
Assuntos
Cordia , Cordia/química , Árvores , Casca de Planta , Excipientes/química , Comprimidos/química , SolubilidadeRESUMO
Immune Cell Deconvolution methods utilizing gene expression profiling to quantify immune cells in tissues and blood are an appealing alternative to flow cytometry. Our objective was to investigate the applicability of deconvolution approaches in clinical trial settings to better investigate the mode of action of drugs for autoimmune diseases. Popular deconvolution methods CIBERSORT and xCell were validated using gene expression from the publicly available GSE93777 dataset that has comprehensive matching flow cytometry. As shown in the online tool, ~ 50% of signatures show strong correlation (r > 0.5) with the remainder showing moderate correlation, or in a few cases, no correlation. Deconvolution methods were then applied to gene expression data from the phase III CLARITY study (NCT00213135) to evaluate the immune cell profile of relapsing multiple sclerosis patients treated with cladribine tablets. At 96 weeks after treatment, deconvolution scores showed the following changes vs placebo: naïve, mature, memory CD4+ and CD8+ T cells, non-class switched, and class switched memory B cells and plasmablasts were significantly reduced, naïve B cells and M2 macrophages were more abundant. Results confirm previously described changes in immune cell composition following cladribine tablets treatment and reveal immune homeostasis of pro- vs anti-inflammatory immune cell subtypes, potentially supporting long-term efficacy.
Assuntos
Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Humanos , Cladribina/uso terapêutico , Cladribina/farmacologia , Imunossupressores/uso terapêutico , Imunossupressores/farmacologia , Linfócitos T CD8-Positivos , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Comprimidos/uso terapêutico , AlgoritmosRESUMO
Three-dimensional (3D) printing technology has presently been explored widely in the field of pharmaceutical research to produce various conventional as well as novel dosage forms such as tablets, capsules, oral films, pellets, subcutaneous implants, scaffolds, and vaginal rings. The use of this innovative method is a good choice for its advanced technologies and the ability to make tailored medicine specifically for individual patient. There are many 3D printing systems that are used to print tablets, implants, and vaginal rings. Among the available systems, the fused deposition modeling (FDM) is widely utilized. The FDM has been regarded as the best choice of printer as it shows high potential in the production of tablets as a unit dose in 3D printing medicine manufacturing. In order to design a 3D-printed tablet or other dosage forms, the physicochemical properties of polymers play a vital role. One should have proper knowledge about the polymer's properties so that one can select appropriate polymers in order to design 3D-printed dosage form. This review highlighted the various physicochemical properties of polymers that are currently used as filaments in 3D printing. In this manuscript, the authors also discussed various systems that are currently adopted in the 3D printing.
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Polímeros , Impressão Tridimensional , Feminino , Humanos , ComprimidosRESUMO
The 2018 European Union (EU) approved weekly and monthly subcutaneous buprenorphine depot injection (BUP-XR), for opioid substitution medication proved to offer some specific treatment benefits. The present study examines the process of switching from buprenorphine sublingual tablets (BUP-SL) to BUP-XR from a patient's point of view. In total, nine patients were surveyed by means of an open-answer questionnaire regarding course and side effects of the medication switch. Six of these patients were surveyed in more detail under BUP-SL, as well as 4 and 16 weeks after the switch to BUP-XR by means of a test battery of questions on socio-demography, withdrawal symptoms, craving, physical well-being, treatment satisfaction and concomitant use of illegal substances. Patients reported significant worse physical well-being and lower treatment satisfaction in 4 weeks compared with 16 weeks after the medication switch to the BUP-XR. Furthermore, they reported significant more frequent co-use of illicit drugs, worse physical well-being, lower treatment satisfaction and more craving experience 4 weeks after the switch compared with the treatment under BUP-SL. Patients 16 weeks under BUP-XR reported significant more illicit co-use and lower treatment satisfaction compared with patients under BUP-SL. Connections between therapy dissatisfaction, physical discomfort, experienced craving and drug co-consumption were discovered. In the first weeks after the medication switch, patients experience potentially distressing symptoms, which, however, seem to diminish over time. Close supervision and comprehensive patient education on possible burdens of the medication switch to the BUP-XR might prevent unfavourable treatment courses and premature therapy dropouts.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Buprenorfina/uso terapêutico , Analgésicos Opioides/uso terapêutico , Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Comprimidos/uso terapêutico , Preparações de Ação Retardada/uso terapêuticoRESUMO
Microcrystalline cellulose (MCC) of different grades from different manufacturers differ in particulate and powder properties significantly. The choice of MCC is important to the development of a tablet formulation with satisfactory quality. In this study, the effects of five different MCCs (KG 802, Pharmacel 102, MC 302, M 200, and PH 112) that had different compactibility and tablet disintegration on the tablet quality of two different natural plant products (NPPs) were evaluated systematically, including Crataegi Folium ethanol extract (CF-E) and Sarcandrae Herba water extract (SH-W). The result of D-optimal mixture designs demonstrated that KG 802 showed the best ability to improve compression properties and tensile strength, followed by Pharmacel 102, MC 302, and M 200. PH 112 did the weakest. However, MCCs of different grades had no different influence on the disintegration of NPP tablets. Similar results were found in the experiments of the two different NPP powders, suggesting the generalization of the finding. Moreover, KG 802-containing CF-E formulations showed the largest optimum region size, that is, the lowest production risk. The design space sizes of SH-W were hardly sensitive to the change of MCCs, due to the better tabletability. In conclusion, the properties of MCCs could transfer to the high NPP loading (70%) formulations, leading to the variations on the compression properties and tablet quality. The poorer the tabletability of NPP, the more obvious the variation. The result is promising for the use of MCC and the manufacturing of high drug-loading NPP tablets by direct compression.
Assuntos
Celulose , Composição de Medicamentos/métodos , Celulose/química , Resistência à Tração , Comprimidos/químicaRESUMO
The sticking of active pharmaceutical ingredient (API) to the surfaces of compaction tooling, frequently referred to as punch sticking, causes costly downtime or product failures in commercial tablet manufacturing. Magnesium stearate (MgSt) is a common tablet lubricant known to ameliorate the sticking problem, even though there exist exceptions. The mechanism by which MgSt lowers punch sticking propensity (PSP) by covering API surface is sensible but not yet experimentally proven. This work was aimed at elucidating the link between PSP and surface area coverage (SAC) of tablets by MgSt, in relation to some key formulation properties and process parameters, namely MgSt concentration, API loading, API particle size, and mixing conditions. The study was conducted using two model APIs with known high PSPs, tafamidis (TAF) and ertugliflozin-pyroglutamic acid (ERT). Results showed that PSP decreases exponentially with increasing SAC by MgSt. The composition of material stuck to punch face was also explored to better understand the onset of punch sticking and the impact of possible MgSt-effected punch conditioning event.
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Ácidos Esteáricos , Composição de Medicamentos/métodos , Pressão , Fenômenos Físicos , ComprimidosRESUMO
BACKGROUND: Good-quality drugs that fulfill the regulatory parameters and are produced per the current good manufacturing practice (cGMP) standards are very critical for the best therapeutic outcomes. However, the variety of branded drugs circulation in the market often put clinicians and pharmacists in a difficult situation of choice due to the possibility of interchangeability among brands, so we should ascertain the quality of the various brands of drugs, available in the drug market. The purpose of the study was to evaluate the quality and physicochemical equivalence of six brands of carbamazepine tablets that are commercially available in Dessie town, Northeast Ethiopia. METHODS: An experimental study design was used. Six different brands of carbamazepine tablets were purchased from community pharmacies in Dessie town, Northeast Ethiopia, which were selected using simple random sampling methods. Identification, weight variation, friability, hardness, disintegration, dissolution test, and assay for the content of active ingredients were evaluated according to the procedures described in the United States Pharmacopeia (USP) and British Pharmacopeia (BP), and the results were compared with USP and BP standards. The difference (f1) and similarity (f2) factors were calculated to assess in vitro bioequivalence requirements. RESULTS: The identification test results revealed that all samples contained the stated active pharmaceutical ingredients and all brands of carbamazepine tablets complied with the official specification for weight variation, friability, and hardness tests. The percentage concentration of carbamazepine was found in the range of 97.85 to 102.09, which met the USP specification of 92% to 108% of the stated amount. Similarly, all samples fulfilled disintegration time (i.e., ≤ 30 min) except brand CA1 (34.183 min) and dissolution tolerance limits (i.e., Q ≥ 75% at 60 min), which was found in the range of 91.673% -97.124%. The difference factor (f1) values were < 15 and the similarity factor (f2) values were > 50 for all the tested brands of carbamazepine tablets. CONCLUSION: The present study revealed that all brands of carbamazepine 200 mg tablets met the quality control parameters as per pharmacopoeial specifications except the disintegration test of brand CA1, and could be used each brand interchangeably to achieve the desired therapeutic effect.
Assuntos
Equivalência Terapêutica , Etiópia , Comprimidos , SolubilidadeRESUMO
Background Difficulty swallowing occurs in up to 35% of patients 50 years of age or older and can contribute to medication nonadherence and other alterations. The use of a flavored lubricating spray, available over-the-counter and found to be helpful in children to swallow oral solid medications, is not well studied in older adults. Objective To evaluate the effect of a flavored lubricating spray on the ability to swallow oral solid medication in older people. Methods A randomized, open-label, crossover study included community-dwelling individuals 65 to 88 years of age who took at least one solid oral medication daily and were not diagnosed with dysphagia, Parkinson's disease, or esophageal tumor. Participants were randomized to the strawberry-flavored lubricating spray or usual care and then crossed over to the alternate option. The median rating for swallowing difficulty for their regular medications was compared using a Likert scale, from 1 (very difficult) to 5 (very easy). To provide a degree of standardization between participants, all participants were also instructed to swallow a vitamin C (1,000 mg) tablet both with and without the flavored spray and rate their difficulty swallowing the tablet using the same Likert scale. Results There were 39 (90.7%) participants who completed the study. The median rating for swallowing difficultly was 5 (very easy) with the spray vs. 4 (easy) with usual care (P < 0.0001). For the 66.7% who took the vitamin C tablets, the median rating for swallowing difficulty was 5 (very easy) with the spray vs. 3.5 (between neutral and easy) without (P < 0.0001). There were 94.8% of participants who found the spray easy/ very easy to use, and 89.7% reported it tasted okay to delicious. Conclusion The use of a flavored lubricating spray provided an effective and easy-to-use tool to make medication swallowing easier in community-dwelling older adults without a diagnosis associated with difficulty swallowing.
Assuntos
Transtornos de Deglutição , Deglutição , Humanos , Idoso , Sprays Orais , Estudos Cross-Over , Transtornos de Deglutição/tratamento farmacológico , Comprimidos/uso terapêuticoRESUMO
In this work, we prepared a novel electrochemical sensor for the detection of tramadol based on a UiO-66-NH2 metal-organic framework (UiO-66-NH2 MOF)/third-generation poly(amidoamine) dendrimer (G3-PAMAM dendrimer) nanocomposite drop-cast onto a glassy carbon electrode (GCE) surface. After the synthesis of the nanocomposite, the functionalization of the UiO-66-NH2 MOF by G3-PAMAM was confirmed by various techniques including X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS), field emission-scanning electron microscopy (FE-SEM), and Fourier transform infrared (FT-IR) spectroscopy. The UiO-66-NH2 MOF/PAMAM-modified GCE exhibited commendable electrocatalytic performance toward the tramadol oxidation owing to the integration of the UiO-66-NH2 MOF with the PAMAM dendrimer. According to differential pulse voltammetry (DPV), it was possible to detect tramadol under optimized circumstances in a broad concentration range (0.5 µM-500.0 µM) and a narrow limit of detection (0.2 µM). In addition, the stability, repeatability, and reproducibility of the presented UiO-66-NH2 MOF/PAMAM/GCE sensor were also studied. The sensor also possessed an acceptable catalytic behavior for the tramadol determination in the co-existence of acetaminophen, with the separated oxidation potential of ΔE = 410 mV. Finally, the UiO-66-NH2 MOF/PAMAM-modified GCE exhibited satisfactory practical ability in pharmaceutical formulations (tramadol tablets and acetaminophen tablets).
Assuntos
Dendrímeros , Grafite , Nanocompostos , Tramadol , Acetaminofen , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier , Composição de Medicamentos , Grafite/química , Nanocompostos/química , Carbono/química , Comprimidos , Técnicas Eletroquímicas/métodosRESUMO
We reported the results of three years of house dust mite sublingual immunotherapy with Miticure® tablets. METHODS: Subjects of 115 cases (63 males, median 12.9 years old, 74 children under 15 years old) were evaluated with Japanese Rhino-conjunctivitis Quality of Life Questionnaire No1 (JRQLQ No1) and visual analog scale (VAS) of 100mm length for rhino-ocular and general symptoms. Annual survey was conducted for three years. RESULTS: Symptoms in all items of 1 to 3 years later by JRQLQ No1 and VAS were significantly improved (p<0.01). There was no difference from 1 year to 3 years later. The VAS value for total symptoms decreased from 41 (18-70) mm before treatment to 10 (4-40) mm after 1 year and 10 (3-30) mm after 3 years (median (IQR)). Concomitant medications used in all patients at the start of treatment were not needed in 60.8% after 1 year and 65.2% after 3 years. After 3 years, 16.5% of the patients were completely cured with no concomitant medication and had a symptom score of 0, and 53.0% were in remission with a score of 1 or less. There was no difference in all items between children and adults, and symptoms improved equally. CONCLUSION: The efficacy of house dust mite sublingual immunotherapy from 1 to 3 years was demonstrated.
Assuntos
Pyroglyphidae , Imunoterapia Sublingual , Adulto , Criança , Masculino , Animais , Humanos , Adolescente , Qualidade de Vida , ComprimidosRESUMO
This study discusses the development and validation of a universal microwell spectrophotometric assay for TKIs, regardless of the diversity in their chemical structures. The assay depends on directly measuring the native ultraviolet light (UV) absorption of TKIs. The assay was carried out using UV-transparent 96-microwell plates and the absorbance signals were measured by a microplate reader at 230 nm, at which all TKIs had light absorption. Beer's law correlating the absorbances of TKIs with their corresponding concentrations was obeyed in the range of 2-160 µg mL-1 with excellent correlation coefficients (0.9991-0.9997). The limits of detection and limits quantitation were in the ranges of 0.56-5.21 and 1.69-15.78 µg mL-1, respectively. The proposed assay showed high precision as the values of the relative standard deviations for the intra- and inter-assay precisions did not exceed 2.03 and 2.14%, respectively. The accuracy of the assay was proven as the recovery values were in the range of 97.8-102.9% (±0.8-2.4%). The proposed assay was successfully applied to the quantitation of all TKIs in their pharmaceutical formulations (tablets) with reliable results in terms of high accuracy and precision. The assay greenness was evaluated, and the results proved that the assay fulfils the requirements of green analytical approach. The proposed assay is the first assay that can analyse all TKIs on a single assay system without chemical derivatization or modifications in the detection wavelength. In addition, the simple and simultaneous handling of a large number of samples as a batch using micro-volumes of samples gave the assay the advantage of high throughput analysis, which is a serious demand in the pharmaceutical industry.
Assuntos
Ensaios de Triagem em Larga Escala , Inibidores de Proteína Tirosina Quinase , Composição de Medicamentos , Espectrofotometria/métodos , Comprimidos/químicaRESUMO
BACKGROUND: No acute treatments targeting calcitonin gene-related peptide (CGRP) have been approved for use in China or South Korea. We aimed to compare the efficacy and safety of rimegepant-an orally administered small molecule CGRP antagonist-with placebo in the acute treatment of migraine among adults in these countries. METHODS: This double-blind, randomised, placebo-controlled, multicentre phase 3 trial was done at 86 outpatient clinics at hospitals and academic medical centres (73 in China and 13 in South Korea). Participants were adults (≥18 years) with at least a 1-year history of migraine who had two to eight moderate or severe attacks per month and fewer than 15 headache days per month within the 3 months before the screening visit. Participants were randomly assigned (1:1) to 75 mg rimegepant or placebo to treat a single migraine attack of moderate or severe pain intensity. Randomisation was stratified by the use of preventive medication and by country. The allocation sequence was generated and implemented by study personnel using an interactive web-response system accessed online from each study centre. All participants, investigators, and the sponsor were masked to treatment assignment. The coprimary endpoints of freedom from pain and freedom from the most bothersome symptom (nausea, phonophobia, or photophobia) 2 h after dosing were assessed in the modified intention-to-treat (mITT) population (randomly assigned participants who took study medication for a migraine attack of moderate or severe pain intensity, and provided at least one efficacy datapoint after treatment) using Cochran-Mantel Haenszel tests. Safety was assessed in all participants who received rimegepant or placebo. The study is registered with ClinicalTrials.gov, number NCT04574362, and is completed. FINDINGS: 1431 participants were randomly assigned (716 [50%] to rimegepant and 715 [50%] to placebo). 668 (93%) participants in the rimegepant group and 674 (94%) participants in the placebo group received treatment. 1340 participants were included in the mITT analysis (666 [93%] in the rimegepant group and 674 [94%] in the placebo group). 2 h after dosing, rimegepant was superior to placebo for pain freedom (132 [20%] of 666 vs 72 [11%] of 674, risk difference 9·2, 95% CI 5·4-13·0; p<0·0001) and freedom from the most bothersome symptom (336 [50%] of 666 participants vs 241 [36%] of 674 participants, 14·8, 9·6-20·0; p<0·0001). The most common (≥1%) adverse events were protein in urine (8 [1%] of 668 participants in the rimepegant group vs 7 [1%] of 674 participants in the placebo group), nausea (7 [1%] of 668 vs 18 [3%] of 674), and urinary tract infection (5 [1%] of 668 vs 8 [1%] of 674). There were no rimegepant-related serious adverse events. INTERPRETATION: Among adults living in China or South Korea, a single dose of 75 mg rimegepant was effective for the acute treatment of migraine. Safety and tolerability were similar to placebo. Our findings suggest that rimegepant might be a useful new addition to the range of medications for the acute treatment of migraine in China and South Korea, but further studies are needed to support long-term efficacy and safety and to compare rimegepant with other medications for the acute treatment of migraine in this population. FUNDING: BioShin Limited. TRANSLATIONS: For the Chinese and Korean translations of the abstract see Supplementary Materials section.
Assuntos
Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Adulto , Humanos , Transtornos de Enxaqueca/diagnóstico , Náusea , Dor , Método Duplo-Cego , Comprimidos/uso terapêutico , China , Resultado do TratamentoRESUMO
BACKGROUND: To better understand the efficacy and safety of Bifidobacterium quadruple viable tablets in the treatment of helicobacter pylori (H. pylori)-infected peptic ulcer or gastritis patients. METHODS: A systematic review of the studies published to June 2022 was performed in English database PubMed, Embase, Chinese database CNKI, Wanfang. There were 17 studies were included in this systematic review and meta-analysis. The outcomes measured included H. pylori eradication rate, changes in clinical symptoms of epigastric pain scores, and the incidence of adverse reactions. RESULTS: The results of the fixed effect model showed that the eradication rate of H. pylori in the combination of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was greater than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (OR = 3.73, 95%CI (2.79,5.00), Z = 2.78, P < 0.001; I2 = 0.0%, P > 0.999). The results of random effects model showed that the epigastric pain score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.70, 95%CI (-1.06,-0.34), Z = 3.82, P < 0.001; I2 = 96.7%, P < 0.001). The results of random effects model showed that the acid reflux score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.98, 95%CI (-1.70,-0.26), Z = 2.66, P < 0.001; I2 = 99.7%, P < 0.001). CONCLUSIONS: The eradication rate of H. pylori by Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing quadruple therapy is better than that of bismuth-containing quadruple therapy. The improvement of clinical symptoms of patients is better than that of bismuth-containing quadruple therapy, and the incidence of adverse reactions is lower than that of bismuth-containing quadruple therapy. Bifidobacterium quadruple viable bacteria tablet combined with bismuth-containing quadruple therapy was effective and safe. It provides a new way to treat patients with H. pylori.
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Gastrite , Helicobacter pylori , Úlcera Péptica , Humanos , Bismuto , Úlcera Péptica/tratamento farmacológico , Dor Abdominal , Bifidobacterium , Gastrite/tratamento farmacológico , ComprimidosRESUMO
Assessing in vivo performance to inform formulation selection and development decisions is an important aspect of drug development. Biopredictive dissolution methodologies for oral dosage forms have been developed to understand in vivo performance, assist in formulation development/optimization, and forecast the outcome of bioequivalence studies by combining them with simulation tools to predict plasma profiles in humans. However, unlike compendial dissolution methodologies, the various biopredictive methodologies have not yet been harmonized or standardized. This manuscript presents the initial phases of an effort to develop best practices and move toward standardization of the biopredictive methodologies through the Product Quality Research Institute (PQRI, https://pqri.org ) entitled "The standardization of in vitro predictive dissolution methodologies and in silico bioequivalence study Working Group." This Working Group (WG) is comprised of participants from 10 pharmaceutical companies and academic institutes. The project will be accomplished in a total of five phases including assessing the performance of dissolution protocols designed by the individual WG members, and then building "best practice" protocols based on the initial dissolution profiles. After refining the "best practice" protocols to produce equivalent dissolution profiles, those will be combined with physiologically based biopharmaceutics models (PBBM) to predict plasma profiles. In this manuscript, the first two of the five phases are reported, namely generating biopredictive dissolution profiles for ibuprofen and dipyridamole and using those dissolution profiles with PBBM to match the clinical plasma profiles. Key experimental parameters are identified, and this knowledge will be applied to build the "best practice" protocol in the next phase.
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Dipiridamol , Ibuprofeno , Humanos , Solubilidade , Comprimidos , Academias e Institutos , Modelos Biológicos , Administração OralRESUMO
Dihydromyricetin (DHM) is an important natural flavonoid. However, most of DHM preparations have shown shortcomings such as low drug loading, poor drug stability, and/or large fluctuations in blood concentration. This study aimed to develop a gastric floating tablet with a double-layered structure for zero-order controlled release of DHM (DHM@GF-DLT). The final product DHM@GF-DLT showed a high average cumulative drug release at 24 h that best fit the zero-order model, and had a good floating ability in the stomach of the rabbit with a gastric retention time of over 24 h. The FTIR, DSC, and XRPD analyses indicated the good compatibility among the drug and the excipients in DHM@GF-DLT. The pharmacokinetic study revealed that DHM@GF-DLT could prolong the retention time of DHM, reduce the fluctuation of blood drug concentration, and enhance the bioavailability of DHM. The pharmacodynamic studies demonstrated that DHM@GF-DLT had a potent and long-term therapeutic effect on systemic inflammation in rabbits. Therefore, DHM@GF-DLT had the potential to serve as a promising anti-inflammatory agent and may develop into a once-a-day preparation, which was favorable to maintain a steady blood drug concentration and a long-term drug efficacy. Our research provided a promising development strategy for DHM and other natural products with a similar structure to DHM for improving their bioavailability and therapeutic effect.
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Flavonóis , Estômago , Animais , Coelhos , Preparações de Ação Retardada/química , Comprimidos/químicaRESUMO
LaVortex® was developed as a novel free-flow continuous granulation/drying (CGD) system. In this study, we compared the advantages and disadvantages of granules prepared by continuous and batchwise manufacturing systems. Granules containing 30 % acetaminophen were manufactured under various operating conditions using CGD system, with comparison granules manufactured using conventional batch systems that involve a combination of fluid bed granulation (FG), agitation granulation (AG), continuous drying, fluid bed drying, and/or shelf drying, after which the pharmaceutical properties of each type of manufactured granule were evaluated. Cumulative particle-size distributions were determined by sieving, powder flowabilities were determined by angle of repose measurements, and scanning electron microscopy was employed to examine granule morphologies. The CGD system produced fine-to-large spherical or ellipsoidal granules that exhibited excellent powder fluidities and tabletabilities that are almost identical to those of AG granules. Moreover, the CGD granules exhibited better powder flowability than the FG granules. The addition of water promoted CGD-granule growth and improved significantly powder flowability, and did a little in tabletability. Small spherical granules with good fluidity suitable for fine-particle-coating core materials, or large granules with excellent fluidity and tabletability, were prepared by adjusting the values of the elemental parameters of the CGD process.
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Acetaminofen , Tecnologia Farmacêutica , Pós , Tamanho da Partícula , Composição de Medicamentos , ComprimidosRESUMO
Enalapril (EN) is an antihypertensive drug that is sparingly soluble in water with limited oral bioavailability. Successfully prepared self-nanoemulsifying systems (SNES) loaded with EN were developed. The solubility of EN in different oils, surfactants, and cosurfactants was tested. Pseudoternary phase diagrams were developed, and various SNES formulations were prepared and evaluated regarding content uniformity, emulsification time, droplet size (DS), and zeta potential (ZP). The selected system was examined using transmission electron microscopy. Solid Self-Nanoemulsifying Systems (SSNES) were formulated using Avicel® PH101 carrier and Aerosil® 200 adsorbent to form a free-flowing powder. The powder was formulated as an oral disintegrating tablet (ODT) using superdisintegrants and tested for physicochemical properties and stability. Finally, an in vivo pharmacokinetic study in healthy human volunteers was carried out. The composition of the selected SNES was 10% Labrafil®, 60% Tween 80, and 30% Transcutol® HP. It developed with an emulsification time of 21 sec, DP range of 60.16 nm, ZP of 1.17 mV, and spherical-shaped globules. The accelerated stability testing proved that there was no significant difference in physical properties after storage for 3 months. The percentage of relative bioavailability for formula F2 was 112.04%. The results of this study proved that the prepared EN-SSNES ODT represents a novel formulation alternative to the currently marketed tablet.
