The aim of the work is devoted to the substantiation of the choice of excipients while the development of Cardiosten tablets with a dry extract from a mixture of medicinal plant materials of ...cardiological action, taking into account the application of the mathematical planning of the experiment. Materials and methods. Using the method of mathematical planning of the experiment (MPE), the influence of auxiliary substances on the technological properties of the granules with dry extract “Cardiosten” and tablets obtained from these granules was investigated. Fillers, sorbents (moisture regulators), structure-forming substances (disintegrating agents), binding substances and calcium stearate as a powdering agent (antifriction substance) were used as excipients. All groups of excipients (except calcium stearate) were divided into levels of factors, which were investigated by the four-factor experiment method based on a Greek-Latin square. The following indicators of granules and tablets based on dry extract “Cardiosen” were used as responses: bulk density g/cm3; mass flow for tableting, s/100g; mass loss during wetting and granulation, %; disintegration of tablets, min., abrasion of tablets, % and resistance of tablets to crushing, N. Results. In the course of the conducted research, the dependence of all responses on the above factors was determined according to the technological parameters of the tablet mass and finished tablets. Based on the analysis of the most effective levels of factors that had the maximum effect on the responses, the following substances were selected as further objects: Prosolv HD 90 (vehicle), Neosorb –100 (sorbent), polyplasdon XL10 (structuring agent) and HPMC solution as a binder. Conclusions. Using the MPE method, the most optimal excipients were selected for the production of tablets with a dry extract content of “Cardiosten”. Based on the indicators of pelletized mass (bulk density, bulk flow, weight loss) and tablets (disintegration time of tablets, abrasion of tablets, resistance of tablets to crushing), the qualitative composition of auxiliary substances for the production of tablets by the method of wet granulation - Prosolv HD 90 (filler) was determined , Neosorb – 100 (sorbent), polyplasdon XL10 (structuring agent), HPMC solution (binding agent).
Debido al uso cada vez masivo de aparatos como tablets o teléfonos celulares equi- pados de un GPS, se incrementó de forma exponencial la cantidad de información georreferenciada producida por los ...usuarios, que puede ser recopilada y difundida a través de Internet. Existen muchas aplicaciones que explotan esta posibilidad de obtener información de cientos o miles de usuarios.
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In this study, we evaluated the palatability of orally disintegrating tablets (ODTs) containing core granules with different particle sizes, coating, and types of materials using ...visual analog scales (VAS). Tableting the core granules into ODTs reduced rough mouth feel and improved overall palatability compared to the ingestion of core granules alone. Moreover, the evaluation performed immediately after spitting out ODTs demonstrated differences in rough mouth feel between ODTs containing placebo and core granules. Rough mouth feel was found to be significantly more intense with core granules with particle sizes ≥200μm. Since ODTs may contain taste-masked particles, palatability of ODTs containing coated core granules was also evaluated. Although coating with polymers impairs palatability, it was improved by coating the outer layer with d-mannitol. The effects on palatability of materials constituting core granules were also evaluated, with reduced rough mouth feel observed with core granules composed of water-soluble additives. Based on these data, receiver operating characteristic analysis was performed to determine the threshold VAS scores at which the subjects felt roughness and discomfort. In addition, the threshold particle size of the core granule contained within the ODT required for feeling roughness was determined to be 244μm. This study elucidated the effect of the properties of masking particles on the rough mouth feel and palatability of ODTs.
Investigation of the effect of disintegrants on the disintegration time and hardness of rapidly disintegrating tablets (RDTs) was carried out using a quality by design (QbD) paradigm. Ascorbic acid, ...aspirin, and ibuprofen, which have different water solubilities, were chosen as the drug models. Disintegration time and hardness of RDTs were determined and modeled by executing combined optimal design. The generated models were validated and used for further analysis. Sodium starch glycolate, croscarmellose sodium, and crospovidone were found to lengthen disintegration time when utilized at high concentrations. Sodium starch glycolate and crospovidone worked synergistically in aspirin RDTs to decrease disintegration time. Sodium starch glycolate-crospovidone mixtures, as well as croscarmellose sodium-crospovidone mixtures, also decreased disintegration time in ibuprofen RDTs at high compression pressures as compared to the disintegrants used alone. The use of sodium starch glycolate in RDTs with highly water soluble active ingredients like ascorbic acid slowed disintegration, while microcrystalline cellulose and crospovidone drew water into the tablet rapidly and quickened disintegration. Graphical optimization analysis demonstrated that the RDTs with desired disintegration times and hardness can be formulated with a larger area of design space by combining disintegrants at difference compression pressures. QbD was an efficient and effective paradigm in understanding formulation and process parameters and building quality in to RDT formulated systems.
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Pediatric, geriatric, and other patients who suffer from swallowing difficulties represent a special patient group, where an increased need in appropriate formulation development is ...required. To overcome these mostly swallowability linked issues, orodispersible tablets (ODTs) and orodispersible mini-tablets (ODMTs) can be seen as a suitable alternative to improve compliance. Orodispersible tablets are oral solid dosage forms which rapidly disintegrate after contact with saliva, leaving a liquid dispersion, which can be easily swallowed. To fulfil the required quality criteria and optimize the formulations regarding tensile strength and disintegration time, co-processed excipients (CPE) based on mannitol are frequently used in the manufacturing of orodispersible tablets. This study aimed to systematically compare two new CPEs, namely Granfiller-D® and Hisorad® and evaluate their potential in future OD(M)T formulations with already marketed products. The performance of the CPEs was examined in combination with three different APIs. Disintegration time, sufficient mechanical strength and content uniformity for low dosed formulation were chosen as main quality aspects. Conventionally sized tablets (9 mm) with 50% drug load of ibuprofen and paracetamol were produced with each CPE. Low dosed OD(M)Ts with a drug load of 4% enalapril maleate were manufactured to study content uniformity. Large differences were visible in the formulations containing ibuprofen and only Hisorad® allowed to compress ODT fulfilling the specifications of Ph.Eur. and FDA regarding disintegration times (180 s and 30 s, respectively). For the poorly binding model drug paracetamol, none of the studied excipients showed a satisfactory performance, with maximum tensile strengths < 1 MPa. To reach content uniformity in low dosed ODMTs, Ludiflash® seems to be the most preferable alternative, as the formulation showed the lowest acceptance values (AV) according to Ph.Eur. (<4) as well as the smallest coefficient of variation (CV) in API content (CV < 2%). In conclusion, the study revealed that none CPE is the ideal choice for all approaches, but different CPEs should be selected dependent on different challenges during formulation development of OD(M)Ts.
The pharmaceutical industry is continually striving to innovate drug development and formulation processes. Orally disintegrating tablets (ODTs) have gained popularity due to their quick release and ...patient-friendly characteristics. The choice of excipients in tablet formulations plays a critical role in ensuring product quality, highlighting its importance in tablet creation. The traditional trial-and-error approach to this process is both expensive and time-intensive. To tackle these obstacles, we introduce a fresh approach leveraging machine learning and deep learning methods to automate and enhance pre-formulation drug design.
We collected a comprehensive dataset of 1983 formulations, including excipient names, quantities, active ingredient details, and various physicochemical attributes. Our study focused on predicting two critical control test parameters: tablet disintegration time and hardness. We compared a range of models like deep learning, artificial neural networks, support vector machines, decision trees, multiple linear regression, and random forests.
A 12-layer deep neural network, as a form of deep learning, surpassed alternative techniques by achieving 73% accuracy for disintegration time and 99% for tablet hardness. This success underscores its efficacy in predicting complex pharmaceutical factors. Such an approach streamlines the drug formulation process, reducing iterations and material consumption.
Our findings highlight the deep learning potential in pharmaceutical formulations, particularly for tablet hardness prediction. Future work should focus on enlarging the dataset to improve model effectiveness and extend its application in pharmaceutical product development and assessment.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Posaconazole tablets, a new oral formulation of posaconazole, can be effective when given as antifungal prophylaxis to neutropenic patients at high risk for invasive fungal infection (e.g., those ...with acute myelogenous leukemia or myelodysplastic syndrome). Such effectiveness might be specifically important to patients with poor oral intake because of nausea, vomiting, or chemotherapy-associated mucositis. This was a prospective, global study in high-risk patients to characterize the pharmacokinetics and safety profile of posaconazole tablets and to identify the dose of posaconazole tablets that would provide exposure within a predefined range of exposures (steady-state average concentration area under the concentration-time curve/24 h of ≥500 ng/ml and ≤2,500 ng/ml in >90% of patients). The study evaluated two sequential dosing cohorts: 200 mg posaconazole once daily (n = 20) and 300 mg posaconazole once daily (n = 34) (both cohorts had a twice-daily loading dose on day 1) taken without regard to food intake during the neutropenic period for ≤28 days. The exposure target was reached (day 8) in 15 of 19 (79%) pharmacokinetic-evaluable patients taking 200 mg posaconazole once daily and in 31 of 32 (97%) patients taking 300 mg posaconazole once daily; 300 mg posaconazole once daily achieved the desired exposure target. Posaconazole tablets were generally well tolerated in high-risk neutropenic patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT01777763.).
In this study, nanoemulsion-based delivery systems fabricated using three different methods were compared with three commercially available curcumin supplements. Powdered curcumin was dispersed into ...the oil-in-water nanoemulsions using three methods: the conventional oil-loading method, the heat-driven method, and the pH-driven method. The conventional method involved dissolving powdered curcumin in the oil phase (60 °C, 2 h) and then forming a nanoemulsion. The heat-driven method involved forming a nanoemulsion and then adding powdered curcumin and incubating at an elevated temperature (100 °C, 15 min). The pH-driven method involved dissolving curcumin in an alkaline solution (pH 12.5) and then adding this solution to an acidified nanoemulsion (pH 6.0). The three commercial curcumin products were capsules or tablets purchased from an online supplier: Nature Made, Full Spectrum, and CurcuWin. Initially, the encapsulation efficiency of the curcumin in the three nanoemulsions was determined and decreased in the following order: pH-driven (93%) > heat-driven (76%) > conventional (56%) method. The different curcumin formulations were then subjected to a simulated gastrointestinal tract (GIT) model consisting of mouth, stomach, and small intestine phases. All three nanoemulsions had fairly similar curcumin bioaccessibility values (74–79%) but the absolute amount of curcumin in the mixed micelle phase was highest for the pH-driven method. A comparison of these nanoemulsions and commercial products indicated that the curcumin concentration in the mixed micelles decreased in the following order: CurcuWin ≈ pH-driven method > heat-driven method > conventional method ≫ Full spectrum > Nature Made. This study provides valuable information about the impact of the delivery system type on curcumin bioavailability. It suggests that encapsulating curcumin within small lipid particles may be advantageous for improving its absorption form the GIT.
Study Objective
To evaluate the impact of pill burden on outcomes in patients with human immunodeficiency virus (HIV) infection and acquired immune deficiency syndrome (AIDS) receiving antiretroviral ...therapy (ART) as a single‐tablet regimen (STR) or multiple‐tablet regimen (MTR).
Design
Retrospective cohort study.
Data Sources
South Carolina Medicaid medical and pharmacy paid claims data were obtained from the South Carolina Revenue and Fiscal Affairs Office; laboratory data were obtained from the South Carolina Department of Health and Environmental Control.
Patients
A total of 2174 patients covered by South Carolina Medicaid who were dispensed a complete ART STR (580 patients) or MTR (1594 patients) lasting at least 60 days between January 1, 2006, and December 31, 2013.
Measurements and Main Results
Outcomes were ART adherence; risk of, time to, and total number of hospitalizations; and viral load suppression. Patients were followed from the index date (start date of their complete ART regimen) until the earliest date of one of the following: treatment discontinuation; treatment switch from MTR to STR, or vice versa; end of study period; last date of Medicaid eligibility; or death. Differences in outcomes were evaluated by using bivariate χ2 and Wilcoxon rank sum tests, as well as multivariate regression models controlling for covariates measured during a 6‐month baseline period. The STR and MTR cohorts were, on average, similar in terms of age at index date, Charlson Comorbidity Index score, sex, drug abuse, and mental health diagnoses, but they differed significantly in racial composition, index year of regimen, previous treatment, baseline viral load, and CD4 measures. The bivariate analysis revealed that the STR cohort was more adherent (p<0.0001), had a lower risk of hospitalization (p=0.0076), and had a higher proportion of patients with viral suppression (64.5% vs 49.5%, p<0.0001). In addition, multivariate regression models revealed that the STR cohort was more adherent and was associated with a lower risk of hospitalization (hazard ratio 0.71, 95% confidence interval 0.59–0.86), but no significant difference in viral load suppression was noted between the STR and MTR cohorts.
Conclusion
The STR was associated with higher adherence rates and a lower risk of hospitalization (both in the adjusted and unadjusted analyses) in South Carolina Medicaid patients with HIV infection and AIDS. A higher proportion of patients in the STR cohort had viral suppression during the follow‐up period in the unadjusted analysis compared with the MTR cohort; however, no significant difference in viral suppression was observed when controlling for adherence.
Greeks wrote mostly on papyrus, but the Romans wrote solemn religious, public and legal documents on wooden tablets often coated with wax. This book investigates the historical significance of this ...resonant form of writing; its power to order the human realm and cosmos and to make documents efficacious; its role in court; the uneven spread - an aspect of Romanization - of this Roman form outside Italy, as provincials made different guesses as to what would please their Roman overlords; and its influence on the evolution of Roman law. An historical epoch of Roman legal transactions without writing is revealed as a juristic myth of origins. Roman legal documents on tablets are the ancestors of today's dispositive legal documents - the document as the act itself. In a world where knowledge of the Roman law was scarce - and enforcers scarcer - the Roman law drew its authority from a wider world of belief.
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