Orodispersible Tablets Research Articles

Comparing budesonide treatment in eosinophilic esophagitis: a specialized center cohort versus a population-based cohort

Objective Eosinophilic esophagitis (EoE) is a chronic immune-mediated disease. The budesonide orodispersible tablet (BOT) is recommended as second-line treatment according to the Danish guideline. This study aimed to compare potential treatment disparities before BOT initiation, follow-up practices, clinico-histologic remission rates during BOT treatment, and adherence to the national guideline between the highly specialized EoE-Cph cohort and the population-based DanEoE cohort. Material and methods This cohort study compared 65 adult patients from the EoE-Cph cohort with 65 patients from the DanEoE cohort. All patients were diagnosed between 2015-2021. The diagnosis of EoE was defined according to the AGREE consensus. Data were extracted manually from medical records and registries. Results In the EoE-Cph cohort, 88% were prescribed proton pump inhibitors (PPIs) before started on BOT compared to 100% in the DanEoE cohort (p = 0.0035). Symptomatic follow-up occurred in 89% of EoE-Cph patients compared to 97% of DanEoE patients after BOT treatment (p = 0.0841). No difference was found between patients who underwent histologic follow-up after topical steroid treatment (83% versus 82%, p = 0.8162). Complete clinico-histologic remission was frequently observed, and no significant difference was observed between the two cohorts (67% versus 80%, p =0.1789). One out of four patients had conflicting symptomatic and histological responses. Conclusions This study did not provide conclusive evidence favoring the treatment of EoE patients exclusively at highly specialized EoE centers. However, the authors acknowledge that further evidence is necessary before considering changes in clinical practice. Conflicting treatment responses, and discontinuation of treatment due to side effects remains a notable concern.

Effects of Glass Bead Size on Dissolution Profiles in Flow-through Dissolution Systems (USP 4).

The effects of glass bead size in the conical space of flow-through cells on the dissolution profiles were investigated in a USP apparatus 4. Dissolution tests of disintegrating and non-disintegrating tablets in flow-through dissolution systems were performed using semi-high precision glass beads with diameters ranging from 0.5mm to 1.5mm. Computational fluid dynamics (CFD) was used to evaluate the effect of shear stress from the dissolution media flow. The use of smaller glass beads in a larger cell resulted in a faster dissolution of the model formulations under certain test conditions. The effect on the dissolution was highly dependent on the size of the beads in the top layer, including those in contact with the tablets. The absence of a bead-size effect on the dissolution of an orodispersible tablet in a small cell can be explained by the floating fragments during the test. CFD analysis showed that smaller bead diameters led to greater shear stress on the tablet, which was correlated with the dissolution rate. Hence, fluid flow through the narrow gaps between the small beads generated strong local flows, causing shear stress. The size of the glass beads used in flow-through cells affects the dissolution rate of tablets by altering the shear stress on the tablets in certain cases (e.g., direct deposition of the formulation on glass beads, large cells, and very low flow rates). Thus, glass bead size must be considered for a robust dissolution test in a flow-through cell system.

Evaluation of the effect of carvedilol orodispersible tablets on ischemia-reperfusion injury and flap viability in rats: An in vivo study.

Flap surgery is an integral part of plastic surgery, and ischemia-reperfusion (I/R) injury significantly affects the viability of the flap. Carvedilol (CRV), a nonselective beta-blocker with alpha-1 blocking and antioxidant properties, and known for its potential in reducing I/R damage, was chosen as the active substance for our study. The aim of this study was to investigate the vasodilator and antioxidant effects of CRV on rat inferior epigastric artery skin flap using orally disintegrating tablets (ODTs). The optimized ODT formulation was subjected to in vivo experiments using Sprague-Dawley female rats (n = 24) divided into three groups: Group I (control, I/R), Group II (treatment, I/R + CRV), and Group III (treatment, I/R), I/R + CRV ODT). Reperfusion was then observed following the release of the microclamp from the pedicle, and the flap was then re-adapted to its original position. Control rats were given oral isotonic solution via gavage and were subjected to 8 h of ischemia and 12 h of reperfusion. Group II was given 2 mg/kg CRV oral tablets for 7 days before and after surgery. Group III was given 2 mg/kg/day CRV ODT for the same period. Biopsies were taken from the flap and histopathological and biochemical analyses including superoxide dismutase, glutathionenitric oxide, malondialdehyde, paraoxonase 1, total oxidant, and total antioxidant capacities were performed. This study demonstrates that CRV ODTs significantly increased flap viability by approximately 25% compared to the control group, highlighting their promising therapeutic potential.

Novel Patient-Friendly Orodispersible Formulation of Ivermectin is Associated With Enhanced Palatability, Controlled Absorption, and Less Variability: High Potential for Pediatric Use.

Ivermectin has been used since the 1980s as an anthelmintic and antiectoparasite agent worldwide. Currently, the only available oral formulation is tablets designed for adult patients. A patient-friendly orodispersible tablet formulation designed for pediatric use (CHILD-IVITAB) has been developed and is entering early phase clinical trials. To inform the pediatric program of CHILD-IVITAB, 16 healthy adults were enrolled in a phase I, single-center, open-label, randomized, 2-period, crossover, single-dose trial which aimed to compare palatability, tolerability, and bioavailability and pharmacokinetics of CHILD-IVITAB and their variability against the marketed ivermectin tablets (STROMECTOL) at a single dose of 12 mg in a fasting state. Palatability with CHILD-IVITAB was considerably enhanced as compared to STROMECTOL. Both ivermectin formulations were well tolerated and safe. Relative bioavailability of CHILD-IVITAB compared to STROMECTOL was estimated as the ratios of geometric means for Cmax, AUC 0-∞, and AUC0-last, which were 1.52 [90% CI: 1.13-2.04], 1.27 [0.99-1.62], and 1.29 [1.00-1.66], respectively. Maximum drug concentrations occurred earlier with the CHILD-IVITAB formulation, with a median Tmax at 3.0 h [range 2.0-4.0 h] versus 4.0 h [range 2.0-5.0 h] with STROMECTOL (P =.004). With CHILD-IVITAB, variability in exposure was cut in half (coefficient of variation: 37% vs 70%) compared to STROMECTOL. Consistent with a more controlled absorption process, CHILD-IVITAB was associated with reduced variability in drug exposure as compared to STROMECTOL. Together with a favorable palatability and tolerability profile, these findings motivate for further clinical studies to evaluate benefits of such a patient-friendly ODT formulation in pediatric patients with a parasitic disease, including infants and young children <15 kg.

Preparation and Evaluation of Anti-Emetic Ginger Orodispersible Tablets from Standardized Extract using Phenolic Profile Effects

Preparation and Evaluation of Anti-Emetic Ginger Orodispersible Tablets from Standardized Extract using Phenolic Profile Effects

Formulation, Development and Optimization of Silymarin Loaded Nanoparticle Orodispersible Tablets for its Anti-inflammatory Activity

The objective of this work was to enhance the anti-inflammatory properties of silymarin by developing and refining an orodispersible tablet formulation loaded with nanoparticles. Formulation development and optimization of silymarin-loaded nanoparticle orodispersible tablet for its anti-inflammatory activity is the focus of this research paper. Nanoparticle drug delivery systems can help to overcome these limitations by enhancing solubility and absorption. Disintegration and dissolution of Orodispersible tablets take place in the mouth rapidly without water, providing a faster onset of action. These nanoparticles were then incorporated into orodispersible tablets containing superdisintegrants and sweeteners using direct compression. A Box-Behnken design was utilized to systematically optimize the tablet formulation based on responses including disintegration time, wetting time, hardness and friability. After 15 minutes, SL-NP Formulation -3, which contains 5% crospovidone as a superdisintegrant, demonstrated maximal drug release, or 98.5%. Rats with paw edema caused by carrageenan were used to test the anti-inflammatory potential. Following three hours, the 400 mg/kg dose showed a strong 48% inhibition; the impact grew to 52% after three hours. Overall, the development of silymarin nanoparticle orodispersible tablets shows promise for improving the anti-inflammatory effects of silymarin through a synergistic combination of nanoencapsulation and rapid disintegrating tablet technologies.

Effectiveness of treatment with budesonide orodispersible tablets in 76 patients with eosinophilic oesophagitis – real-life experience from the population-based DanEoE cohort

Background Eosinophilic oesophagitis (EoE) is a chronic immune-mediated disease. In Denmark, the budesonide orodispersible tablet (BOT) is recommended as a second-line treatment for proton pump inhibitor-refractory EoE patients. Aims To evaluate the effectiveness of treatment with BOT in adult EoE patients in a population-based setting in Denmark. Methods This was a retrospective, registry-based, DanEoE cohort study of all 76 adult EoE patients treated with BOT and diagnosed between 2007 and 2021 in the North Denmark Region. After medical record revision, the EoE diagnosis was defined according to the AGREE consensus. Symptomatic response was based on the information found in the patients’ medical reports and histologic remission was defined as <15 eosinophils per high-power field (eos/hpf). Results Histologic remission was achieved in 89% of the patients treated with BOT who underwent histologic evaluation. Clinicohistologic remission was achieved in 71% of the patients who underwent both symptomatic and histologic evaluation. Despite histologic remission, 18% of patients still experienced symptoms. Non-responders were found in 7% of the patients. Complications were rare, with dilation of strictures performed in 7% and food bolus obstruction (FBO) occurring in 3%. Discontinuation of the treatment due to unacceptable side effects was observed in 11% of the treated patients. Conclusions Treatment with BOT effectively induced histologic remission in most of the EoE patients. Despite achieving histologic remission, approximately 1/5 of the patients were still symptomatic. Complications were rare. In non-responders and those with unacceptable side effects, alternative treatment options such as biologic agents might be needed.

Prophylactic endoscopic vacuum therapy for stricture prevention following wide-field endoscopic submucosal dissection of superficial esophageal cancer

Background and aimsEsophageal stricture (ES) is a severe adverse event following wide-field endoscopic submucosal dissection (ESD) of superficial esophageal carcinoma. This study evaluated the efficacy and safety of combining endoscopic vacuum therapy (EVT) and budesonide orodispersible tablet (BOT) in preventing post-ESD strictures. MethodsThis prospective case series included patients with superficial esophageal squamous cell carcinoma and adenocarcinoma who had wide-field ESD (≥75% circumference, resection length ≥50 mm). After ESD, EVT was applied immediately, followed by 8 weeks of BOT. The main outcome measurement was the incidence of post-ESD stricture. ResultsEleven patients underwent ESD. Of these, 81.8% had 75-99% circumference resected, and 18.2% had a circumferential resection. EVT remained in situ for a mean of 3.5 days. No esophageal strictures were observed by the final follow-up. There were no major adverse events related to EVT or BOT. ConclusionsThe prophylactic combination of EVT and BOT is a novel and promising strategy for reducing post-ESD strictures.

Solubility enhancement of etoricoxib using inclusion complexation with cyclodextrins: formulation of oro dispersible tablets by QbD approach

Background: The work was intended to enhance etoricoxib's solubility and dissolution rate and then develop oro-dispersible tablets for faster onset of action. Methodology: Inclusion complexes (ICs) of the drug were obtained with β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP β-CD) at ratios of 1:0.125, 1:0.25, 1:0.5, 1:1, and 1:2 (w/w). The selected cyclodextrin at appropriate drug carrier proportion was used to develop oro-dispersible tablets (ODTs) by direct compression, adding crospovidone as a super disintegrant. Phase solubility studies of etoricoxib were carried out by using multiple concentrations of β-cyclodextrin and hydroxypropyl β-cyclodextrin, i.e., 1 %, 2 %, 3 % w/v in distilled water at 37±2°C. Spectroscopic (FT-IR) and thermal analysis (DSC) techniques were employed to identify the drug-carrier interactions. Result: It showed that etoricoxib solubility improves with increasing hydrophilic carrier concentration. The Gibbs free energy values (ΔG˚tr) are consistently negative, showing the solubility of etoricoxib. Significant drug carrier interaction in spectroscopic or thermal analysis was not found. Discussion: The ICs of drugs with β-CD and HP β-CD have successfully addressed the challenges of solubility enhancement and taste masking for etoricoxib. Conclusions: It is observed that the inclusion complexes formed by the kneading method using β-cyclodextrin (β-CD) at a 1:1 ratio and hydroxypropyl β-cyclodextrin (HP β-CD) at a 1:2 ratio can be used to improve dissolution. Hence β-CD (at a 1:1 ratio) is selected for the formulation of oro-dispersible tablets. ODTs offer more patient compliance and an alternative to available conventional tablets.

Formulation and optimization of olanzapine-carboxylic acid cocrystals orodispersible tablets: In-vitro/ In-vivo study

Oromucosal delivery of olanzapine (OLZ) is an optimal strategy to overcome low oral bioavailability as well as improve medication adherence. However, its poor aqueous solubility may hinder its absorption through the buccal mucosa. The aim of the study is to enhance OLZ solubility and dissolution via cocrystal formation, followed by incorporation into an orodispersible tablet (ODT) based on an effervescent mixture and crospovidone as a superdisintegrant mixture. OLZ was cocrystallized with different carboxylic acids using slow solvent evaporation, and the optimal cocrystal formula was subjected to solid state characterization. Central composite design (CCD) was used in the modeling and optimization of the ODT independent variables (amounts of crospovidone and effervescent mixture). The optimized OLZ cocrystal ODTs were subjected to microenvironmental pH, stability, and in-vivo studies. The results revealed that the OLZ:itaconic acid at 1:1 M ratio showed a 7.86 fold increase in OLZ solubility and 86.71 ± 1.07 % dissolution efficiency (DE60 %) with FTIR, XRPD, and DSC diffractograms that confirmed the cocrystal formation. The optimized OLZ cocrystal ODTs exhibited hardness of 3.6 ± 0.1 kg/cm2, disintegration time of 11.66 ± 1.52 s, wetting time of 36.33 ± 2.51 s, and 94.26 ± 2.77 % OLZ released within 15 min with a DE60 % of 91.65 ± 0.98 %. Finally, the optimized OLZ cocrystal ODTs showed a significant (p < 0.01) higher Cmax and AUC with a relative bioavailability of 139.08 % compared to the Schisolazine©10 mg ODTs. These results suggest that OLZ:itaconic acid cocrystal incorporated into an ODT containing a superdisintegrant mixture of effervescence mixture and crospovidone is a potential approach for enhancement of oromucosal delivery of OLZ.

Development of Orodispersible Tablets with Solid Dispersions of Fenofibrate and Co-Processed Mesoporous Silica for Improved Dissolution.

Poor water solubility is an important challenge in the development of oral patient-friendly solid dosage forms. This study aimed to prepare orodispersible tablets with solid dispersions of a poorly water-soluble drug fenofibrate and a co-processed excipient consisting of mesoporous silica and isomalt. This co-processed excipient, developed in a previous study, exhibited improved flow and compression properties compared to pure silica while maintaining a high specific surface area for drug adsorption. Rotary evaporation was used to formulate solid dispersions with different amounts of fenofibrate, which were evaluated for solid state properties and drug release. The solid dispersion with 30% fenofibrate showed no signs of crystallinity and had a significantly improved dissolution rate, making it the optimal sample for formulation or orodispersible tablets. The aim was to produce tablets with minimal amounts of additional excipients while achieving a drug release profile similar to the uncompressed solid dispersion. The compressed formulations met the requirements for orodispersible tablets in terms of disintegration time, and the drug release from best formulation approximated the profile of uncompressed solid dispersion. Future research should focus on reducing the disintegration time and tablet size to enhance patient acceptability further.

Bioequivalence and Safety of Bilastine 20 mg Orodispersible Tablets and Conventional Tablets: A Randomized, Single-Dose, Two-Period Crossover Study in Healthy Volunteers Under Fasting Conditions.

Orodispersible tablets (ODT) rapidly dissolve in the oral cavity and can improve patient's convenience. This pharmacokinetic study assessed the bioequivalence of a novel 20 mg ODT formulation of bilastine compared with bilastine 20 mg tablets in healthy volunteers under fasting conditions. A phase I, single-center, open-label, two-period, two-sequence crossover randomized clinical trial was conducted. The study comprised two periods, in which participants were administered a single oral dose of bilastine 20 mg in the form of ODT as the test product, or conventional tablets as the reference product, and a washout of 7 days between each period. Blood samples were collected for up to 72 h. Bioequivalence was established if the 90% confidence intervals of the Cmax and AUC0-t were within the acceptance range (80-125%). Safety was evaluated at the follow-up visit (days 4-7 after the second dose) and throughout the study. A total of 42 healthy volunteers were randomized, and 41 completed the study. Pharmacokinetic parameters were comparable for both formulations after a single dose of 20 mg. Bilastine ODT and conventional tablets were bioequivalent as the 90% confidence intervals of the test over reference ratios were within the predefined range (80-125%). Both formulations were well tolerated and showed a similar safety profile. Bilastine ODT was bioequivalent to the reference treatment formulated as conventional tablets when administered as a single oral dose of 20 mg under fasting conditions. Both formulations showed a similar tolerability and safety profile, with no serious adverse events or significant analytical alterations reported. 2019-004071-39. Date of authorization: 10 December 2019.

Orodispersible Dosage Forms with Rhinacanthin-Rich Extract as a Convenient Formulation Dedicated to Pediatric Patients.

Rhinacanthins, derived from Rhinacanthus nasutus, widely used in traditional medicine, exhibit antifungal, anticancer, antiviral, antibacterial, and antiplatelet aggregation effects. Recently, their anti-diabetic activity was confirmed, which makes them an interesting natural alternative in the therapy of the early stage of diabetes mellitus. The aim of this study was to demonstrate the possibility of formulating orodispersible tablets (ODTs) and orodispersible films (ODFs) containing rhinacanthin-rich extract (RRE). Tablets with 50 mg or 100 mg of RRE were produced by direct compression. ODFs were manufactured by casting of Lycoat RS 720 or polyvinyl alcohol solution with RRE and additional excipients. The mechanical properties and disintegration times of the prepared formulations were studied. The effectiveness of taste masking was analyzed with an electronic tongue system. Six months simplified stability studies were performed in conditions complying to ICH guidelines. Appropriate friability of ODTs was achieved, despite low tensile strength (0.45-0.62 MPa). All prepared ODFs successfully met the acceptance criteria regarding Young's modulus, tensile strength, and elongation at break. The observed variations in their mechanical properties were dependent on the type and quantity of polymers and plasticizers used. Disintegration time of ODTs ranged from 38.7 s to 54.2 s, while for ODFs from 24.2 to 40 s in the pharmacopoeial apparatus. Analyses made with the electronic tongue showed the significant taste-masking effect in both formulations. The addition of sucralose as a sweetener and menthol with mint flavor as a taste-masking agent was sufficient to mask an RRE's taste in the case of ODTs and ODFs. Stability studies of ODTs packed in the PVC/Alu blisters showed a decrease in the RRE content below 90% after 6 months. However, ODFs with PVA were physicochemically stable for 6 months while being stored in Alu/Alu sachets. Our study proved for the first time the possibility of the formulation of orodispersible dosage forms with RRE, characterized by good mechanical properties, disintegration time, and appropriate taste masking.

Real-world effectiveness and safety of combined calcium 600 mg and cholecalciferol 2000 IU for treating vitamin D deficiency: Results from a nationwide study with focus in osteoporosis

IntroductionTreatment of calcium (Ca) and vitamin D (VD) deficiency (VDD) is crucial for health, especially in bone conditions, such as low bone mineral density (BMD) and osteoporosis. Despite updates in clinical guideline recommendations, no studies have evaluated the efficacy and safety of administering 2000 IU of cholecalciferol combined with calcium. Thus, the main objective of this study was to evaluate VD levels following treatment with Ca 600 mg/ cholecalciferol 2000 IU in real-life clinical practice. MethodsThis multicenter, retrospective, observational study included 302 adult patients receiving Ca 600 mg/D3 2000 IU orodispersible tablets, daily for ≥24 weeks. The primary outcome was 25-hydroxivitamin D [25(OH)D] serum levels following treatment. Key secondary outcomes included changes in serum 25(OH)D levels and other bone metabolism (BM) parameters, safety and tolerability. The protocol was approved by a Research Ethics Committee. Results285 patients were evaluated (mean age [SD]: 67.4 [12.6] years old; 88.4 % women; basal serum 25(OH)D: 20.0 [8.6] ng/mL); 80.7 % reported previous history of osteoporosis/low BMD (osteopenia) and 37.2 % had received other Ca/VD prior to start study treatment. Median treatment duration was 38.5 weeks [range 24.0–82.4]. Overall, 94.4 % of patients increased serum 25(OH)D following treatment to a mean of 36.3 [11.8] ng/mL (p < 0.001 vs. baseline). Patients with basal VDD, significantly increased serum 25(OH)D to a mean over 30 ng/mL; no significant change found in repleted patients (basal 25(OH)D level ≥ 30 ng/mL). PTH was significantly reduced after treatment, with no clinically relevant effect on serum Ca or phosphate. Three non-serious treatment-emergent adverse events were reported. A post-hoc analysis on osteoporotic patients revealed virtually identical results in this population. ConclusionTreatment with Ca 600 mg/cholecalciferol 2000 IU for at least 24 weeks is effective and safe, especially in osteoporosis. Patients with VDD significantly increase plasma 25(OH)D to optimal range for bone health, with no clinically relevant changes on other bone metabolism parameters other than reducing secondary hyperparathyroidism. The magnitude of 25(OH)D increase directly correlates with the severity of VDD, with no effect in basally repleted patients.

Design and evaluation of cost-effective oro-dispersible tablets of venlafaxine hydrochloride by effervescent method

Design and evaluation of cost-effective oro-dispersible tablets of venlafaxine hydrochloride by effervescent method

Formulation and Evaluation of pH-Modulated Amorphous Solid Dispersion-Based Orodispersible Tablets of Cefdinir.

Cefdinir (CEF) is a semi-synthetic third-generation broad-spectrum oral cephalosporin that exhibits poor solubility at lower pH values. Considering this, pH-modulated CEF solid dispersions (ASDs) were produced by solvent evaporation method employing various hydrophilic carriers and alkalizers. Among different carriers, ASDs produced using PEG 6000 with meglumine as alkalizer were found to significantly increase (p < 0.005) the drug solubility (4.50 ± 0.32 mg/mL) in pH 1.2. Fourier transform infrared spectrophotometry confirmed chemical integrity of CEF while differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) indicated CEF was reduced to an amorphous state in ASD8. Antimicrobial assay performed by well diffusion method against Staphylococcus aureus (MTCC96) and Escherichia coli (MTCC118) demonstrated significantly superior (p < 0.001) efficacy of CEFSD compared to CEF. The porous orodispersible tablets (ODTs) of ASD8 (batch F5) were developed by incorporating ammonium bicarbonate as a subliming agent by direct compression, followed by vacuum drying displayed quick disintegration (27.11 ± 1.96 s) that met compendial norms and near-complete dissolution (93.85 ± 1.27%) in 30 min. The ODTs of ASD8 appear to be a promising platform to mitigate the pH-dependent solubility and dissolution issues associated with CEF in challenging physiological pH conditions prevalent in stomach. Thus, ODTs of ASD8 are likely to effectively manage various infections and avoid development of drug-resistant strains, thereby improving the curing rates.

Current Drug Delivery Strategies to Design Orally Dissolving Formulations to Target Tuberculosis: A Futuristic Review

Abstract: All the standard anti-tubercular drugs, well established as standard therapy, are preferentially available in formulations compliant with the young adult population. However, their use in the paediatric and geriatric populations is confronted with issues, such as a high likelihood of incorrect dose administration due to practices like dosage form fracture and splitting. This may lead to drug resistance due to misuse and in-accurate dosage administration, the most dreaded and difficult-to-treat stage of tuberculosis. : Poor patient compliance and adherence are major issues with the conventional line of therapy. This burden may be more significant in resource-constrained settings, necessitating the creation of simple formulations that are both geriatric and child-friendly. An extensive literature survey has been conducted in this study using databases of Google Scholar, PubMed, and Research Gate, with a focus on specific research works on oro-dispersible films, tablets, and wafer technology loaded with anti-tuberculosis drugs from 2022 to 2010. : Mouth dissolving formulation technology is a very novel approach in the arena of tuberculosis therapy. This may pave the way for future researchers to develop different mouth dissolving formulations to treat both pulmonary and extra-tuberculosis. This review paper has summarized all the formulation approaches alongside the present state of the art in tuberculosis therapy using mouth dissolving formulations.

Formulation Development and Optimization of Orodispersible Tablet of Loratadine

Loratadine, a histamine H1 receptor antagonist, is used to treat urticaria and allergic rhinitis. Children who have trouble swallowing tablets make it difficult to administer loratadine orally. F1-F9 batches of Loratadine Tablets (ODTs) 10 mg dose were developed and tested in the present research. In this research, super disintegrants such as croscarmellose sodium, sodium starch glycolate, and crosspovidone were used to manufacture fast-dissolving tablets utilising the direct compression method. In phosphate buffer pH 6.8, the impact of various super disintegrants on tablet dissolving behaviour was examined.

Leading Paediatric Infectious Diseases-Current Trends, Gaps, and Future Prospects in Oral Pharmacotherapeutic Interventions.

Paediatric infectious diseases contribute significantly to global health challenges. Conventional therapeutic interventions are not always suitable for children, as they are regularly accompanied with long-standing disadvantages that negatively impact efficacy, thus necessitating the need for effective and child-friendly pharmacotherapeutic interventions. Recent advancements in drug delivery technologies, particularly oral formulations, have shown tremendous progress in enhancing the effectiveness of paediatric medicines. Generally, these delivery methods target, and address challenges associated with palatability, dosing accuracy, stability, bioavailability, patient compliance, and caregiver convenience, which are important factors that can influence successful treatment outcomes in children. Some of the emerging trends include moving away from creating liquid delivery systems to developing oral solid formulations, with the most explored being orodispersible tablets, multiparticulate dosage forms using film-coating technologies, and chewable drug products. Other ongoing innovations include gastro-retentive, 3D-printed, nipple-shield, milk-based, and nanoparticulate (e.g., lipid-, polymeric-based templates) drug delivery systems, possessing the potential to improve therapeutic effectiveness, age appropriateness, pharmacokinetics, and safety profiles as they relate to the paediatric population. This manuscript therefore highlights the evolving landscape of oral pharmacotherapeutic interventions for leading paediatric infectious diseases, crediting the role of innovative drug delivery technologies. By focusing on the current trends, pointing out gaps, and identifying future possibilities, this review aims to contribute towards ongoing efforts directed at improving paediatric health outcomes associated with the management of these infectious ailments through accessible and efficacious drug treatments.

Drug dissolution and transit in a heterogenous gastric chyme after fed administration: Semi-mechanistic modeling and simulations for an immediate-release and orodispersible tablets containing a poorly soluble drug

Mathematical models that treat the fed stomach content as a uniform entity emptied with a constant rate may not suffice to explain pharmacokinetic profiles recorded in clinical trials. In reality, phenomena such as the Magenstrasse or chyme areas of different pH and viscosity, play an important role in the intragastric drug dissolution and its transfer to the intestine. In this study, we investigated the data gathered in the bioequivalence trial between an immediate-release tablet (Reference) and an orally dispersible tablet (Test) with a poorly soluble weak base drug administered with or without water after a high-fat high-calorie breakfast. Maximum concentrations (Cmax) were significantly greater after administering the Reference product than the Test tablets, despite similar in vitro dissolution profiles. To explain this difference, we constructed a novel semi-mechanistic IVIVP model including a heterogeneous gastric chyme. The drug dissolution in vivo was modeled from the in vitro experiments in biorelevant media simulating gastric and intestinal fluids in the fed state (FEDGAS and FeSSIF). The key novelty of the model was separating the stomach contents into two compartments: isolated chyme (the viscous food content) that carries the drug slowly, and aq_chyme open for rapid Magenstrasse-like routes of drug transit. Drug distribution between these two compartments was both formulation- and administration-dependent, and recognized the respective drug fractions from the clinical pharmacokinetic data. The model’s assumption about the nonuniform mixing of the API with the chyme, influencing differential drug dissolution and transit kinetics, led to simulating plasma concentration profiles that reflected well the variability observed in the clinical trial. The model indicated that, after administration, the Reference product mixes to a greater extent with aq_chyme, where the released drug dissolves better and transfers faster to the intestine. In conclusion, this novel approach underlines that diverse gastric emptying of different oral dosage forms may significantly impact pharmacokinetics and affect the outcomes of bioequivalence trials.