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The development of suitable dosage forms is essential for an effective pharmacological treatment in children. Orally disintegrating tablets (ODTs) are attractive dosage forms that avoid swallowing problems, ensure dosage accuracy and are easy to administer as they disintegrate in the oral cavity. This study aimed to develop ODTs containing losartan potassium (LP) for the treatment of arterial hypertension in children. The ODTs, produced by the cost-effective manufacturing process of direct compression, consisted of a mixture of diluent, superdisintegrant, glidant and lubricant. Five superdisintegrants (croscarmellose sodium, two grades of crospovidone, sodium starch glycolate and pregelatinized starch) were tested (at two concentrations), and combined with three diluents (mannitol, lactose and sorbitol). Thus, thirty formulations were evaluated based on disintegration time, hardness and friability. Two formulations, exhibiting the best results concerning disintegration time (< 30 s), hardness and friability (≤ 1.0%), were selected as the most promising ones for further evaluation. These ODTs presented favourable drug-excipient compatibility, tabletability and flow properties. The in vitro dissolution studies demonstrated 'very rapid' drug release. Preliminary stability studies highlighted the requirement of a protective packaging. All quality properties retained appropriate results after 12 months of storage in airtight containers. In conclusion, the ODTs were successfully developed and characterised, suggesting a potential means to accomplish a final prototype that enables an improvement in childhood arterial hypertension treatment.

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The use of herbal medicine to treat various diseases is becoming increasingly important as an alternative therapy. Numerous plants have been traditionally used for different purposes, including antiparasitic in humans and animals. Diseases caused by gastrointestinal parasites in ruminants, especially by the nematode Haemonchus contortus, cause large economic losses to the producers, whether by complications of the diseases or the cost of treatment. The main way of handling nematodiasis is by administering anthelmintic drugs, but their excessive use has the disadvantage of causing drug resistance; therefore, an alternative is the use of herbal medicine for this purpose. Mesquite (Prosopis spp.) has been used in Mexico to treat gastrointestinal diseases attributed to helminths. The present study aimed to characterize the rheological properties of mesquite flour using the SeDeM Expert System to determine its suitability for tablet production by direct compression. Direct compression technology facilitates the tableting process by reducing manufacturing costs. The results of the present study indicate that mesquite flour can be processed by direct compression. The latter could allow the manufacturing of economic tablets to treat infections by H. contortus in ruminants.

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Along with the United States Pharmacopeia (USP) chapters 232 and 233 regarding elemental impurities in pharmaceutical products, new challenges have been imposed in terms of sample preparation procedures prior to inductively coupled plasma mass spectrometry analysis, considering the matrix complexities. As so, a new microextraction procedure assisted by ultrasound using a cup-horn sonoreactor, minimal reactants, and sample was proposed and validated according to USP. The procedure was optimized with samples of milled tablets and 3 different acid mixtures (HNO3, 3HNO3:1HCl, and 9HNO3:1HF) and it was compared with microwave-assisted acid digestion. In the validation step, recoveries ranging from 85 to 120 % and RSD below 10 % were obtained for 22 analytes (except Ag and Pt) with satisfactory linearity and good sensitivity. The method was then applied for 37 samples of antidepressants, which presented trace levels of As, Ba, Cd, Co, Cr, Cu, Ni, Pb, Pd, Sn, and V.

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Paracetamol, a contaminant of emerging concern, has been detected in different bodies of water, where it can impact ecological and human health. To quantify this paracetamol, electroanalytical methods have gained support. Thus, the present study developed a simple, inexpensive, and environmentally friendly method for paracetamol quantification using a carbon fiber microelectrode based on commercial carbon fiber. To improve the carbon fiber microelectrode's paracetamol sensitivity and selectivity, it was subjected to an activation process via electrochemical oxidation in an acid medium (H2SO4 or HNO3), using 20 consecutive cycles of cyclic voltammetry. The treated (activated) carbon fiber microelectrode was characterized using scanning electron microscopy and electrochemical techniques, including chronoamperometry and electrochemical impedance spectroscopy. The H2SO4-activated carbon fiber microelectrode exhibited enhanced figures of merit, with a linear dynamic range of paracetamol detection from 0.5 to 11 µmol L-1 and a limit of detection of 0.21 µmol L-1 under optimized conditions. The method was optimized by quantifying paracetamol in commercial pharmaceutical tablets, spiked running tap water, and river water (Pita River, Quito, Ecuador, latitude -0.364955°, longitude -78.404538°); the respective recovery values were 102.89, 103.93, and 112.40%. The results demonstrated an acceptable level of accuracy and the promising applicability of this carbon fiber microelectrode as a sensor to detect paracetamol.

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Cognitive assessment is a fundamental step in diagnosing intellectual and developmental disabilities, designing interventions, and evaluating their impact. However, developed and developing countries have different access to tools designed for these purposes. Our goal was to develop a battery for cognitive assessment mediated by digital technology that allows the exploration of cognitive domains (inhibitory control, attention, motor ability, and context memory) in children with Down Syndrome (DS) in Chile. Four tasks, based on established experimental paradigms modified to provide a game-like experience, were tested in 68 children with DS from 20 months to 12 years of age. We present evidence of reliability based on internal consistency and split-half analyses, with results ranging from adequate to excellent. Regarding validity, factorial and correlational analyses show evidence consistent with what was theoretically expected of internal structure, convergence, and divergence with other measures. Expected age trajectories were observed as well. Our data offer evidence that supports the use of tasks based on touch-screen devices for cognitive assessment in the population with DS. The tasks also have a low cultural load, so they could be validated and used in other contexts without the need for an adaptation process.

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Abstract The aim of this study was to compare the dissolution properties of ibuprofen solid oral dosage forms commercially available in Bosnia and Herzegovina and to estimate the influence of dissolution medium composition on the drug release. Eight products (A-H) were subjected to in vitro dissolution test using experimental conditions described in USP42-NF37. Dissolution properties of one selected product were examined in the presence of alcohol (22.2% v/v) and fruit juice (22.2% v/v). Products marked B-H complied with the pharmacopeial criteria. Dissolution profile of product B was similar with dissolution profiles of products D, E, F and G and similarity was also found between products A-D, C-G, D-G and E-F. Drug release from most of the examined preparations fitted best to the Weibull kinetic model. In the presence of alcohol in the medium, higher amount of ibuprofen was dissolved. Contrary, ibuprofen dissolved in the presence of fruit juice was significantly lower. Differences in the dissolution profiles of investigated preparations suggest that their interchangeability should be additionally considered and demonstrated with in vivo bioequivalence studies. Presence of different substances in the medium can affect dissolution properties of ibuprofen, emphasizing the importance of the patient's compliance.

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Anthocyanins obtained from jambolan have been used as active agents in different carboxymethyl starch-based tablet formulations and their release profiles evaluated in simulated gastric fluids (SGF) and simulated intestinal (SIF) fluids. Structural analysis highlighted a strong interaction between anthocyanins and carboxymethyl starch, evidenced by scanning electron microscopy and infrared analysis. Tablet dissolution behavior varied according to the pH of the media, being controlled by the swelling and/or erosion of the polymeric matrix. Various formulations for immediate, fast, and sustained release of anthocyanins for 30 min, 2 h and 12 h of dissolution have been developed. It was found that monolithic carboxymethyl starch tablets loaded with powdered jambolan extract efficiently afforded the complete delivery (100% of anthocyanins) to different sites of the simulated gastrointestinal tract and ensured the stability of these pigments, which maintained their antioxidant activity.

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Three-dimensional (3D) printing has been gaining attention as a new technological approach to obtain immediate release (IR) dosage forms. The versatility conferred by 3D printing techniques arises from the suitability of using different polymeric materials in the production of solids with different porosities, geometries, sizes, and infill patterns. The appropriate choice of polymer can facilitate in reaching IR specifications and afford other specific properties to 3D printed solid dosage forms. This review aims to provide an overview of the polymers that have been employed in the development of IR 3D printed dosage forms, mainly considering their in vitro drug release behaviour. The physicochemical and mechanical properties of the IR 3D printed dosage forms will also be discussed, together with the manufacturing process strategies. Up to now, methacrylic polymers, cellulosic polymers, vinyl derivatives, glycols and different polymeric blends have been explored to produce IR 3D printed dosage forms. Their effects on drug release profiles are critically discussed here, giving a complete overview to drive formulators towards a rational choice of polymeric material and thus contributing to future studies in 3D printing of pharmaceuticals.

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The development of extended-release dosage forms with adequate drug release is a challenge for pharmaceutical companies, mainly when the drug presents high solubility, as in Biopharmaceutics Classification System (BCS) class I. This study aimed to develop extended-release mini-tablets containing metoprolol succinate (MS), while integrating design of experiments (DOE) and physiologically based biopharmaceutics modeling (PBBM), to predict its absorption and to run virtual bioequivalence (VBE) studies in both fasted and fed states. Core mini-tablet formulations (F1, F2, and F3) were prepared by direct compression and coated using nine coating formulations planned using DOE, while varying the percentages of the controlled-release and the pore-forming polymers. The coated mini-tablets were submitted to a dissolution test; additional formulations were prepared that were optimized by simulating the dissolution profiles, and the best one was submitted to VBE studies using GastroPlus® software. An optimized formulation (FO) containing a mixture of immediate and extended-release mini-tablets showed to be bioequivalent to the reference drug product containing MS when running VBE studies in both fasted and fed states. The integration of DOE and PBBM showed to be an interesting approach in the development of extended-release mini-tablet formulation containing MS, and can be used to rationalize the development of dosage forms.

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This study used grounded theory to investigate older Uruguayans' use of tablets delivered through a public program called Plan Ibirapitá. This program was developed in 2015, by the leftist government that was in power at that time, to promote the digital inclusion of individuals considered to be excluded from the benefits of the information society, such as older adults. Through Plan Ibirapitá, older adults who receive a pension below approximately 900 USD, receive a tablet for free, training for its use, and 1 GB of monthly internet. According to the program's Fifth-Use Survey from 2019, almost 60% of those who received Plan Ibirapitá's tablet do not use it. To examine the relationship between older adults and the tablets, twenty-six participants were interviewed about their experiences with this device. Results suggest that the relationship they established with the tablets is ambivalent. On the one hand, the participants see information and communication technology (ICT) as modern tools that are useful for communicating with loved ones. On the other hand, they understood their lives as busy for which tablets were mostly unnecessary. These findings indicate that including older people into the digital world is more complex than distributing devices top-down.

Key Points: Digital inclusion is complex and should not be based on technological determinism.Top-down technological programs need to consider older people's social contexts.Policymakers should avoid technological-solutionist approaches to problems of aging.Older people are not necessarily nor automatically benefited by digital technology.Provides a background for technological-intervention programs in other countries.

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Abstract The current investigation was used to improve the rate of dissolution of an anti-diarrheal drug i.e., racecadotril (RT) at low pH conditions (i.e., in the stomach) by reducing the water secretion and electrolyte in to the intestine by liquisolid tablets. Different formulations (liquisolid) were prepared using Avicel PH 102 as a carrier. Aerosil 200 as a coating material and sodium starch glycolate used as a disintegrant. Polyethylene glycol 200 was used as a non-volatile vehicle to dissolve the drug. FTIR, DSC, XRD and dissolution studies were conducted to characterise liquisolid tablets. Characterisation studies indicated that no interactions between carrier and drug. Solid state characterization had shown a reduction in crystallinity that further supports increment in solubility and dissolution. The optimised formulation showed a significant increase in dissolution i.e., 99.54±0.62% in 30 min compared to directly compressible tablets (38.47±0.26%). The % dissolution efficiency of racecadotril liquisolid tablets 76.86% compared to marketed tablet (27.56%) and conventional direct compression tablet (17.11%). Significant reduction in mean dissolution time of racecadotril from liquisolid tablets (6.84 min) compared to direct compression tablet (44.57 min), indicating faster release of drug and faster onset of action. Formulation of liquisolid tablets could enhance solubility, dissolution and bioavailability of racecadotril

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Abstract Quality is paramount and needs to be maintained throughout the shelf life of pharmaceuticals. The current study aimed to evaluate the quality, potency, and drug-drug interaction in an in vivo animal model by using two drugs, namely, metoprolol and glimepiride. Tablets were selected for their physical characteristics, such as shape, size, and color. Quality control tests, such as weight variation, hardness, friability, and disintegration tests, and invitro drug release studies were performed as per USP. Drug-drug interaction and in vivo studies were carried out according to the standard protocol of the animal ethics committee. Quality control tests of both the tablets were within the specified range. The cumulative release percentages of the drugs were 81.12% and 85.36% for Metoprolol Tartrate and Glimepiride, respectively, in a physiological buffer solution within 1 h. The combination of metoprolol and Glimepiride also significantly decreased the blood glucose level in diabetic animals. However, the blood glucose level increased in the group receiving metoprolol only, but the difference was not significant. The result suggested that the formulations are safe. However, the chronic use of this combination requires frequent monitoring of blood glucose level to improve its efficacy and for the patient's safety.

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The purpose of this work was to elaborate a diagnosis of the dissolution test in Africa in comparison with Brazil, evaluating the dissolution profile of low solubility drugs such as albendazole, ibuprofen, furosemide, glibenclamide, hydrochlorothiazide and carvedilol to ascertain their quality. The dissolution profiles were evaluated by utilizing the United States Pharmacopeia (USP). The glibenclamide medicine was evaluated according to the Food and Drug Administration (FDA), while a dissolution method was developed for the carvedilol medicine. A filter selection test for all the drugs showed that cannula is suitable for all, except for carvedilol, which is centrifuged. The various brands of Nigerian and Brazilian medicines tested showed some statistical differences. The suitable conditions that allowed the dissolution of carvedilol to be determined were the USP type II apparatus at 75 rpm containing 900 mL of acetate buffer, pH 4.5. The results of the dissolution test showed that out of the 17 different brands of Brazilian medicines and 17 different products from Nigeria, 94.12% and 58.82% passed respectively

O objetivo deste trabalho foi elaborar um diagnóstico do teste de dissolução na África em comparação ao Brasil, avaliando o perfil de dissolução de medicamentos de baixa solubilidade como albendazol, ibuprofeno, furosemida, glibenclamida, hidroclorotiazida e carvedilol para verificar sua qualidade.Os perfis de dissolução foram avaliados utilizando a Farmacopeia dos Estados Unidos (USP). O medicamento glibenclamida foi avaliado de acordo com a Food and Drug Administration (FDA), enquanto um método de dissolução foi desenvolvido para o medicamento carvedilol.Um teste de seleção de filtro para todos os medicamentos mostrou que a cânula é adequada para todos, exceto para o carvedilol, que é centrifugado. As diversas marcas de medicamentos Nigerianos e Brasileiros testadas apresentaram algumas diferenças estatísticas. As condições adequadas que permitiram a determinação da dissolução do carvedilol foram o aparelho USP tipo II a 75 rpm contendo 900 mL de tampão acetato, pH 4,5. Os resultados do teste de dissolução mostraram que das 17 diferentes marcas de medicamentos brasileiros e 17 diferentes produtos da Nigéria, 94,12% e 58,82% foram aprovados, respectivamente

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Abstract Hydralazine hydrochloride is an anti-hypertensive drug. The drug has poor oral bioavailability (BA) of about 30- 50% due to extensive first-pass metabolism. Hence, the buccal delivery was used to enhance the BA of hydralazine hydrochloride. Buccal muco-adhesive tablets were prepared by direct compression technique, using carbopol 934P, HPMC K4M, sodium alginate and sodium carboxy methyl cellulose (NaCMC) as muco-adhesive polymers. Prepared formulations were evaluated for physico-chemical characterization, ex-vivo residence time and in-vitro release studies. The some of the parameters viz hardness, thickness, weight variation are showing the values within the pharmacopeial limits. However, the swelling and bio-adhesive strength were increased with increasing polymer concentrations. From the in-vitro release studies, F9 buccal tablets prepared with NaCMC exhibited better release (96.56%, 6 h) profile than all other formulations and considerd as optimized. The release mechanism from kinetic methods suggests that, the drug release follows zero-order kinetics with diffusion mechanism. Thus, the buccal tablets of hydralazine hydrochloride showed enhanced BA and were further confirmed by in-vivo studies.

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Abstract The objective of the present investigation was to design, optimize and characterize the gastro retentive floating levofloxacin tablets and perform in-vivo evaluation using radiographic imaging. The floating tablets were prepared by using polymers i.e hydroxy propyl methyl cellulose (HPMC-K4M) and carbopol-940 individually and in combination by nonaquous granulation method. All the Formulations were evaluated for swelling index (S.I), floating behavior and in-vitro drug release kinetics. The compatibility study of levofloxacin with other polymers was investigated by FTIR, DSC, TGA and XRD. Results from FTIR and DSC revealed no chemical interaction amongst the formulation components. The optimized formulation (F11) showed floating lag time (FLT), total floating time (TFT) swelling index (S.I) of 60 sec, >16h and approximately 75 %, respectively. Moreover, F11 showed zero order levofloxacin release in simulated gastric fluid over the period of 6 h. X-ray studies showed that total buoyancy time was able to delay the gastric emptying of levofloxacin floating tablets in rabbits for more than 4 hours. In conclusion the optimized formulation (F11) can be used for the sustained delivery of levofloxacin for the treatment of peptic ulcer.

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Eudragit® polymers are polymethacrylates highly used in pharmaceutics for the development of modified drug delivery systems. They are widely known due to their versatility with regards to chemical composition, solubility, and swelling properties. Moreover, Eudragit polymers are thermoplastic, and their use has been boosted in some production processes, such as hot melt extrusion (HME) and fused deposition modelling 3D printing, among other 3D printing techniques. Therefore, this review covers the studies using Eudragit polymers in the development of drug delivery systems produced by HME and 3D printing techniques over the last 10 years. Eudragit E has been the most used among them, mostly to formulate immediate release systems or as a taste-masker agent. On the other hand, Eudragit RS and Eudragit L100-55 have mainly been used to produce controlled and delayed release systems, respectively. The use of Eudragit polymers in these processes has frequently been devoted to producing solid dispersions and/or to prepare filaments to be 3D printed in different dosage forms. In this review, we highlight the countless possibilities offered by Eudragit polymers in HME and 3D printing, whether alone or in blends, discussing their prominence in the development of innovative modified drug release systems.

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OBJECTIVE: The objective of this work was to prepare mucoadhesive buccal tablets containing nystatin and purified cashew gum for the treatment of oral candidiasis. SIGNIFICANCE: Mucoadhesive buccal tablets containing the drug nystatin are an alternative to oral suspensions, which cause low therapeutic adherence to the treatment of oral candidiasis. Purified cashew gum has been studied as a diluent and mucoadhesive agent in tablets. METHODS: Two batches of mucoadhesive tablets were produced, MT1 and MT 2, containing purified cashew gum, nystatin (500,000 IU), flavoring agent and with or without the presence of lubricant agent. The average weight, mechanical properties, dose uniformity, drug release profile, mucoadhesive properties and antimicrobial activity against Candida albicans were evaluated. RESULTS: Tablets presented average weight of 329.1 ± 3.1 mg (MT1) and 334.6 ± 1.5 mg (MT2), hardness of 9.8 ± 0.8 KgF (MT1) and 8.3 ± 0.4 KgF (MT2), friability of 0.2% (MT1 and MT2), and dose uniformity of 102.20 ± 1.17% (MT1) and 99.06 ± 7.40% (MT2). MT1 and MT2 were able to swell, erode, release the drug and remain adhered to the pig's cheek up to 3 h for batch MT1 and 4 h for batch MT2, and the amount of nystatin released since the beginning of the test in both batches was sufficient to inhibit the growth of the fungus. CONCLUSIONS: Therefore, the proposed formulation proved to be very promising and met all the studied criteria, showing to be ideal for the treatment of oral candidiasis.

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PURPOSE: To investigate the impact of peroxide-based solutions in reducing viability and metabolic activity of multispecies biofilms on denture base acrylic resin surfaces and for removing them from these surfaces. BACKGROUND: Denture cleansers are effective in reducing monospecies biofilm; however, studies evaluating their action on multispecies biofilms are scarce. MATERIALS AND METHODS: Sixty-nine denture base acrylic resin specimens (Ø 15 × 3 mm) were sterilised then contaminated with Candida albicans, Staphylococcus aureus and Pseudomonas aeruginosa to form multispecies biofilms. Biofilms were grown for 24 hours; subsequently, specimens were immersed in three different cleansing solutions (n = 9): nitradine (NI), fixodent (FX) and phosphate-buffered saline (Control), according to the respective manufacturer's instructions. After applying the hygiene protocols, viability of microorganisms was evaluated by counting colony-forming units and assessing metabolic activity. Moreover, biofilm removal capacity was estimated based on extension of cell-covered areas visualised in fluorescent microscopy micrographics. RESULTS: Microbial counts were solution-dependent; NI was effective against all microorganisms (P < .05). FX exhibited moderate antimicrobial action, reducing P aeruginosa (P < .05) and S aureus (P < .05) viability by approximately 2 logs. Both peroxide-based solutions reduced metabolic activity (P < .001) and biofilm-covered areas on specimen surfaces (P < .001). CONCLUSION: Under the experimental conditions tested, these results demonstrated that peroxide-based solutions had favourable antimicrobial activity but promoted no broad elimination of aggregated multispecies biofilm. NI might be more suitable as complementary chemical agent for controlling multispecies denture biofilm.

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OBJECTIVES: This study was designed to evaluate the clinical efficacy of controlled-release morphine tablets combined with celecoxib in relieving osteocarcinoma-related pain and the effects of the combination on WNK1 expression. METHODS: A total of 110 patients with osteocarcinoma-related pain were selected and divided into two groups based on the treatment administered, including the control group (treated with controlled-release morphine tablets alone) and the study group (treated with a combination of controlled-release morphine tablets and celecoxib). We compared the treatment efficacy, pain level (visual analog scale (VAS)), time of onset of breakthrough pain (BTP), dose of morphine, incidence of adverse events, quality of life (QOL) score, and With-no-lysine 1 (WNK1) expression in the peripheral blood (PB) as determined with qRT-PCR before and after treatment, of the two groups. RESULTS: The total effective rate of the study group was higher than that of the control group, while the VAS score, time of onset of BTP, dose of morphine, incidence of adverse events, QOL score, and relative WNK1 expression in the PB were lower than those of the control group (p<0.05). CONCLUSION: Combination treatment with controlled-release morphine tablets and celecoxib can be extensively used in the clinical setting because it effectively improves the symptoms, QOL score, and adverse effects in patients with osteocarcinoma-related pain.

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BACKGROUND: Health care costs are growing faster than the rest of the global economy, according to the World Health Organization (WHO). Countries' health expenditures include paying for general medicine, diagnostic procedures, hospitalizations and surgeries, as well as medications and prescribed treatment. Primary biliary cholangitis (PBC) is a rare autoimmune liver disease and the first line available treatment is ursodeoxycholic acid (UDCA), however, direct and indirect treatment costs are expensive. Main aim of this trial was to assess if the therapeutic efficacy of UDCA manufactured by the university hospital is equivalent to that of standard UDCA and treatment cost reduction in patients with PBC. METHODS: It is a prospective, interventional, randomized, and crossover study in patients diagnosed with PBC. UDCA 300 mg tablets and capsules were developed and manufactured by the university hospital. Thirty patients under treatment with standard UDCA, in stable doses were randomized in sequence A and B, 15 patients in each arm. The groups were treated for 12 weeks and after, the UDCA formulation was changed, following for another 12 weeks of continuous therapy (tablets and capsules / capsules and tablets). Laboratory tests were performed at time T0 (beginning of treatment), T1 (at the 12 week-therapy, before the crossing-over) and T2 (end of treatment). The evaluation was done by comparing the hepatic parameters ALP, GGT, ALT, AST and total bilirubin, also considering the adverse events. The comparison of costs was based on price of the manufactured UDCA and standard UDCA price of the hospital. RESULTS: Hospital reduced 66.1% the PBC treatment costs using manufactured UDCA. There were no differences in the biochemical parameters between sequence (A and B) and tablets or capsules of UDCA formulations applied in the treatment of PBC. CONCLUSIONS: The study showed that there was no significant difference between manufactured UDCA (capsule and tablet) and standard UDCA. Hospital reduced the PBC treatment costs using the manufactured UDCA by the university hospital. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03489889 retrospectively registered on January 12th, 2018; Ethics Committee approved the study (ID: 1.790.088) on October 25th, 2016.

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