Gastrointestinal Drug Research Articles

Investigating the Impact of Tablet Coatings on Gastrointestinal Tract Residence Time and Drug Bioavailability: A Comparative Study of Different Coating Materials

Tablet coatings are crucial for optimizing pharmaceutical formulations by controlling drug release, stability, and bioavailability. The selection of coating material must be tailored to the specific pharmacokinetic properties and therapeutic goals of the drug. This study focuses on three major types of coatings: enteric polymers, lipid-based coatings, and nanoparticle coatings, each offering unique benefits for different drug delivery systems on Gastrointestinal (GSI). Enteric polymers protect drugs from gastric degradation, ensuring targeted release in the intestines, making them ideal for pH-sensitive drugs. Lipid-based coatings are effective for sustained-release formulations, providing controlled drug release over extended periods, which is particularly beneficial for managing chronic conditions. Nanoparticle coatings offer precise drug delivery, allowing for targeted treatment with reduced systemic side effects, and are especially valuable in oncology for delivering chemotherapeutic agents directly to tumor cells. The choice of coating material is guided by preclinical and clinical studies, which evaluate the physicochemical properties, solubility, stability, and permeability of coating materials under simulated gastrointestinal conditions. Advances in nanotechnology and predictive modeling are transforming drug delivery systems, providing opportunities for hybrid coatings that combine the strengths of different materials. These developments promise enhanced precision, scalability, and efficiency in drug formulation. This study highlights the importance of aligning coating properties with therapeutic goals and emphasizes the potential for hybrid systems, 3D printing, and nanotechnology to create more effective, patient-centric drug delivery solutions. Such innovations are expected to improve therapeutic outcomes, reduce dosing frequency, and enhance patient adherence, ultimately advancing the field of drug delivery and improving patient care.

Cephalopod-inspired jetting devices for gastrointestinal drug delivery

Needle-based injections currently enable the administration of a wide range of biomacromolecule therapies across the body, including the gastrointestinal tract1, 2–3, through recent developments in ingestible robotic devices4, 5, 6–7. However, needles generally require training, sharps management and disposal, and pose challenges for autonomous ingestible systems. Here, inspired by the jetting systems of cephalopods, we have developed and evaluated microjet delivery systems that can deliver jets in axial and radial directions into tissue, making them suitable for tubular and globular segments of the gastrointestinal tract. Furthermore, they are implemented in both tethered and ingestible formats, facilitating endoscopic applications or patient self-dosing. Our study identified suitable pressure and nozzle dimensions for different segments of the gastrointestinal tract and applied microjets in a variety of devices that support delivery across the various anatomic segments of the gastrointestinal tract. We characterized the ability of these systems to administer macromolecules, including insulin, a glucagon-like peptide-1 (GLP1) analogue and a small interfering RNA (siRNA) in large animal models, achieving exposure levels similar to those achieved with subcutaneous delivery. This research provides key insights into jetting design parameters for gastrointestinal administration, substantially broadening the possibilities for future endoscopic and ingestible drug delivery devices.

A Case Series of Fixed Drug Combination of Esomeprazole and Levosulpride Associated Akathisia

Abstract Gastric symptoms are very common and often associated with gastrointestinal (GI) disorders and other systemic disorders. Several drugs such as esomeprazole and levosulpiride are often used in the management of these symptoms. However, there are reports suggesting an association between specific GI drug combination and the development of akathisia with them. These case series aim to investigate and document the cases of the fixed drug combination of esomeprazole- and levosulpiride-associated akathisia, highlighting this potential adverse effect. This combination is rarely reported to cause akathisia in the literature. Whenever this combination is prescribed, patients and their caregivers should be warned of symptoms of akathisia.

Dihydropyrimidine Dehydrogenase Polymorphism c.2194G>A Screening Is a Useful Tool for Decreasing Gastrointestinal and Hematological Adverse Drug Reaction Risk in Fluoropyrimidine-Treated Patients.

Although the risk of fluoropyrimidine toxicity may be decreased by identifying poor metabolizers with a preemptive dihydropyrimidine dehydrogenase (DPYD) test, following international standards, many patients with wild-type (WT) genotypes for classic variations may still exhibit adverse drug reactions (ADRs). Therefore, the safety of fluoropyrimidine therapy could be improved by identifying new DPYD polymorphisms associated with ADRs. This study was carried out to assess whether testing for the underestimated c.2194G>A (DPYD*6 polymorphism, rs1801160) is useful, in addition to other well-known variants, in reducing the risk of ADRs in patients undergoing chemotherapy treatment. This retrospective study included 132 patients treated with fluoropyrimidine-containing regimens who experienced ADRs such as gastrointestinal, dermatological, hematological, and neurological. All subjects were screened for DPYD variants DPYD2A (IVS14+1G>A, c.1905+1G>A, rs3918290), DPYD13 (c.1679T>G, rs55886062), c.2846A>T (rs67376798), c.1236G>A (rs56038477), and c.2194G>A by real-time polymerase chain reaction (RT-PCR). In this cohort, the heterozygous c.2194G>A variant was present in 26 patients, while 106 individuals were WT; both subgroups were compared for the incidence of ADRs. This assessment revealed a high incidence of gastrointestinal and hematological ADRs in DPYD6 carriers compared to WT. Moreover, we have shown a higher prevalence of ADRs in females compared to males when stratifying c.2194G>A carrier individuals. Considering that c.2194G>A was linked to clinically relevant ADRs, we suggest that this variant should also be assessed preventively to reduce the risk of fluoropyrimidine-related ADRs.

Bridging in silico and in vitro perspectives to unravel molecular mechanisms underlying the inhibition of β-glucuronidase by coumarins from Hibiscus trionum

Unraveling the intricacies of β-glucuronidase inhibition is pivotal for developing effective strategies in applications specific to gastrointestinal health and drug metabolism. Our study investigated the efficacy of some Hibiscus trionum phytochemicals as β-glucuronidase inhibitors. The results showed that cleomiscosin A and mansonone H emerged as the most potent inhibitors, with IC50 values of 3.97 ± 0.35 μM and 10.32 ± 1.85 μM, respectively. Mechanistic analysis of β-glucuronidase inhibition indicated that cleomiscosin A and the reference drug EGCG displayed a mixed inhibition mode against β-glucuronidase, while mansonone H exhibited noncompetitive inhibition against β-glucuronidase. Docking studies revealed that cleomiscosin A and mansonone H exhibited the lowest binding affinities, occupying the same site as EGCG, and engaged significant key residues in their binding mechanisms. Using a 30 ns molecular dynamics (MD) simulation, we explored the interaction dynamics of isolated compounds with β-glucuronidase. Analysis of various MD parameters showed that cleomiscosin A and mansonone H exhibited consistent trajectories and significant energy stabilization with β-glucuronidase. These computational insights complemented experimental findings, underscoring the potential of cleomiscosin A and mansonone H as β-glucuronidase inhibitors.

Ionic Polymerization-Based Synthesis of Bioinspired Adhesive Hydrogel Microparticles with Tunable Morphologies from Microfluidics.

Shape-anisotropic hydrogel microparticles have attracted considerable attention for drug-delivery applications. Particularly, nonspherical hydrogel microcarriers with enhanced adhesive and circulatory abilities have demonstrated value in gastrointestinal drug administration. Herein, inspired by the structures of natural suckers, we demonstrate an ionic polymerization-based production of calcium (Ca)-alginate microparticles with tunable shapes from Janus emulsion for the first time. Monodispersed Janus droplets composed of sodium alginate and nongelable segments were generated using a coflow droplet generator. The interfacial curvatures, sizes, and production frequencies of Janus droplets can be flexibly controlled by varying the flow conditions and surfactant concentrations in the multiphase system. Janus droplets were ionically solidified on a chip, and hydrogel beads of different shapes were obtained. The in vitro and in vivo adhesion abilities of the hydrogel beads to the mouse colon were investigated. The anisotropic beads showed prominent adhesive properties compared with the spherical particles owing to their sticky hydrogel components and unique shapes. Finally, a novel computational fluid dynamics and discrete element method (CFD-DEM) coupling simulation was used to evaluate particle migration and contact forces theoretically. This review presents a simple strategy to synthesize Ca-alginate particles with tunable structures that could be ideal materials for constructing gastrointestinal drug delivery systems.

Global burden of vaccine-associated hepatobiliary and gastrointestinal adverse drug reactions, 1967-2023: A comprehensive analysis of the international pharmacovigilance database.

Although previous studies have focused on hepatobiliary and gastrointestinal adverse drug reactions (ADRs) associated with COVID-19 vaccines, literature on such ADRs with other vaccines is limited, particularly on a global scale. Therefore, we aimed to investigate the global burden of vaccine-associated hepatobiliary and gastrointestinal ADRs and identify the vaccines implicated in these occurrences. This study utilized data from the World Health Organization (WHO) international pharmacovigilance database to extract reports of vaccine-associated hepatobiliary and gastrointestinal ADRs from 1967 to 2023 (total reports = 131 255 418). Through global reporting counts, reported odds ratios (ROR) with 95% confidence interval (CI), and information components (IC) with IC0.25, the study examined the association between 16 vaccines and the incidence of hepatobiliary and gastrointestinal ADRs across 156 countries. Of the 6 842 303 reports in the vaccine-associated ADRs, 10 786 reports of liver injury, 927 870 reports of gastrointestinal symptoms, 2978 reports of pancreas and bile duct injury, and 96 reports of intra-abdominal hemorrhage between 1967 and 2023 were identified. Most hepatobiliary and gastrointestinal ADRs surged after 2020, with the majority of reports attributed to COVID-19 messenger RNA (mRNA) vaccines. Hepatitis A vaccines exhibited the highest association with liver injury (ROR [95% CI]: 10.30 [9.65-10.99]; IC [IC0.25]: 3.33 [3.22]), followed by hepatitis B, typhoid, and rotavirus. Specifically, ischemic hepatitis had a significant association with both Ad5-vectored and mRNA COVID-19 vaccines. Gastrointestinal symptoms were associated with all vaccines except for tuberculosis vaccines, particularly with rotavirus (11.62 [11.45-11.80]; 3.05 [3.03]) and typhoid (11.02 [10.66-11.39]; 3.00 [2.96]). Pancreas and bile duct injury were associated with COVID-19 mRNA (1.99 [1.89-2.09]; 0.90 [0.83]), MMR (measles, mumps, and rubella), and papillomavirus vaccines. For intra-abdominal hemorrhage, inactivated whole-virus COVID-19 vaccines (3.93 [1.86-8.27]; 1.71 [0.41]) had the highest association, followed by COVID-19 mRNA (1.81 [1.42-2.29]; 0.77 [0.39]). Most of these ADRs had a short time to onset, within 1 day, and low mortality rate. Through a global scale database, the majority of ADRs occurred within 1 day, emphasizing the importance of healthcare workers' vigilant monitoring and timely management.

Stability of starch-folic acid/ polyethylene glycol particles for gastrointestinal drug delivery

This study takes a novel approach by exploring the potential of starch/polyethylene glycol core/shell particles, where folic acid was encapsulated, as effective gastrointestinal drug delivery systems. The results demonstrate the successful encapsulation of folic acid within the starch/PEG particles, with sizes ranging from 18 to 45 μm depending on the type of starch used (corn, potato, rice). Importantly, applying PEG coating had no negative impact on cell viability and did not induce alterations in fibroblast morphology. The investigation of stability in gastric and intestinal fluids revealed that the particles underwent different degrees of degradation. In simulated gastric fluid, a partial degradation of the PEG layer by 30–37% was observed, while the starch-folic acid core remained intact. However, the PEG layer underwent a 50% degradation in simulated intestinal fluid. This degradation of the PEG layer allowed the controlled and gradual release of folic acid. These findings underscore the role of fluid composition in influencing the stability and degradation behavior of the particles, with significant implications for their functionality as drug delivery systems in the gastrointestinal tract.

Type 1 diabetes human enteroid studies reveal major changes in the intestinal epithelial compartment

Lack of understanding of the pathophysiology of gastrointestinal (GI) complications in type 1 diabetes (T1D), including altered intestinal transcriptomes and protein expression represents a major gap in the management of these patients. Human enteroids have emerged as a physiologically relevant model of the intestinal epithelium but establishing enteroids from individuals with long-standing T1D has proven difficult. We successfully established duodenal enteroids using endoscopic biopsies from pediatric T1D patients and compared them with aged-matched enteroids from healthy subjects (HS) using bulk RNA sequencing (RNA-seq), and functional analyses of ion transport processes. RNA-seq analysis showed significant differences in genes and pathways associated with cell differentiation and proliferation, cell fate commitment, and brush border membrane. Further validation of these results showed higher expression of enteroendocrine cells, and the proliferating cell marker Ki-67, significantly lower expression of NHE3, lower epithelial barrier integrity, and higher fluid secretion in response to cAMP and elevated calcium in T1D enteroids. Enteroids established from pediatric T1D duodenum identify characteristics of an abnormal intestinal epithelium and are distinct from HS. Our data supports the use of pediatric enteroids as an ex-vivo model to advance studies of GI complications and drug discovery in T1D patients.

Development of Physiologically Based Biopharmaceutical Model (PBBM) for Felodipine Prolonged-Release Tablet as useful tool for prediction of formulation.

Physiologically Based Biopharmaceutical Models (PBBMs) are advanced tools that integrate physiological parameters with drug-specific properties to simulate drug behavior in vivo. In this study, we present the development of a PBBM specifically tailored for felodipine prolonged-release (PR) tablet formulations. Felodipine, a potent calcium channel blocker, is widely used for the treatment of hypertension and angina pectoris. Prolonged-release formulations aim to provide controlled drug release, ensuring sustained therapeutic effect with reduced dosing frequency and minimized adverse effects. Our PBBM incorporates key physiological processes such as gastrointestinal transit, drug dissolution, absorption, distribution, metabolism, and elimination. Data from in vitro dissolution studies, preclinical pharmacokinetics, and clinical observations are integrated to parameterize the model accurately. Special attention is given to the physicochemical properties of felodipine and the release characteristics of the PR tablet formulation. Validation of the PBBM is conducted against clinical pharmacokinetic data obtained from bioequivalence studies and population pharmacokinetic analyses of felodipine PR tablets. The model may demonstrate excellent predictive performance, accurately capturing plasma concentration-time profiles across different dosing regimens and patient populations. The developed PBBM provides valuable insights into the biopharmaceutical behavior of felodipine PR tablets, facilitating rational formulation design, dosage regimen optimization, and therapeutic individualization. It serves as a powerful tool for drug developers, regulatory agencies, and clinicians to enhance the efficiency and effectiveness of drug development and clinical pharmacotherapy

Proton pump inhibitors use is associated with a higher prevalence of kidney stones: NHANES 2007–2018

BackgroundProton pump inhibitors (PPIs) are widely used throughout the world as an effective gastrointestinal drug. Nevertheless, according to the existing literature, PPIs can reduce the excretion of magnesium, calcium and other components in urine, which may promote the formation of kidney stones. We used the National Health and Nutrition Examination Survey (NHANES) database to further investigate the association between the use of PPIs and the prevalence of kidney stones.MethodsWe performed a cross-sectional analysis using data from 2007 to 2018 NHANES. PPIs use information of 29,910 participants was obtained by using prescription medications in the preceding month, and kidney stones were presented by a standard questionnaire. Multiple regression analysis and stratified analysis were used to estimate the association between PPIs use and kidney stones after an adjustment for potential confounders.ResultsThe multiple logistic regression indicated that the PPIs exposure group (P1) had a significantly higher risk of nephrolithiasis than the PPIs non-exposure group (P0) in Model 3 (OR 1.24, 95% CI 1.10–1.39, P < 0.001). The stratified analyses indicated there were significant statistical differences between PPIs use and kidney stones among females (OR 1.36, 95% CI 1.15–1.62, P < 0.001), non-Hispanic whites (OR 1.27, 95% CI 1.09–1.48, P = 0.002), individuals with an education level than 11th grade (OR 1.41, 95% CI 1.13–1.76, P = 0.002) and individuals with an annual family income of $0 to $19,999 (OR 1.32, 95% CI 1.06–1.65, P = 0.014) and $20,000 to $44,999 (OR 1.25, 95% CI 1.02–1.54, P = 0.033) in Model 3.ConclusionsOur study revealed that PPIs use is associated with a higher prevalence of kidney stones for the US population, primarily among women, non-Hispanic whites, individuals with low education levels and individuals with low household income levels. Further studies are required to confirm our findings.

Impact of Anti Tubercular Drugs on Biochemical Changes in Newly Diagnosed Tuberculosis Patients

Background: The disease tuberculosis (TB) continues to be a major global health concern, with high rates of morbidity and mortality, particularly in developing nations. It affects multiple organs and has the ability to alter metabolic processes. The purpose of this study was to ascertain how patients' serum biochemical markers were affected by tuberculosis and the medications used to treat it. Objective: The aim of this study is to evaluate impact of anti-tubercular drugs on biochemical changes in newly diagnosed tuberculosis patients. Methods: The cross-sectional observational study was conducted in Netrokona Medical College Hospital, Netrokona, from 1st January 2022 to 31st December 2023. A total of 120 newly diagnosed cases of pulmonary tuberculosis were enrolled and analyzed in this study. The questionnaire was pretested, corrected and finalized. Data were collected by face-to-face interview and analyzed by appropriate computer based programmed software Statistical Package for the Social Sciences (SPSS), version 24. Results: In this study, majority 48 (40.0%) of the patients were in 31 - 40 years age group and 28 (23.3%) patients were in 41 - 50 years age group, Mean±SD of age was 36.13±11.03 years. Most of the patients 69 (57.50%) were male and 51 (42.50%) patients were female. Most of the patients 87 (72.5%) were in normal range (18.5 – 29.9 kg/m2), 15 (11.7%) of the patients were underweight (&lt;18.5) and 19 (15.8%) of the patients were overweight (&gt;30). Serum Glutamic Oxaloacetic Transaminase and Serum Glutamic Pyruvic Transaminase level were 18.00 (4.01), 21.04 (3.16) before treatment but after treatment the level became 20.10 (3.52), 22.57 (4.41). Urea and Creatinine level were 18.20 (2.31), 0.63 (0.15) before treatment but after treatment 20.01 (5.34) and 0.53 (0.13). After treatment by anti-tubercular drug gastrointestinal adverse drug effects were nausea 3 (2.5%), vomiting 6 (5.0%), diarrhea 3 (2.5%) and abdominal pain 5 (4.2%), followed by itching ......

Protein Coronas Derived from Mucus Act as Both Spear and Shield to Regulate Transferrin Functionalized Nanoparticle Transcellular Transport in Enterocytes.

The epithelial mucosa is a key biological barrier faced by gastrointestinal, intraoral, intranasal, ocular, and vaginal drug delivery. Ligand-modified nanoparticles demonstrate excellent ability on this process, but their efficacy is diminished by the formation of protein coronas (PCs) when they interact with biological matrices. PCs are broadly implicated in affecting the fate of NPs in vivo and in vitro, yet few studies have investigated PCs formed during interactions of NPs with the epithelial mucosa, especially mucus. In this study, we constructed transferrin modified NPs (Tf-NPs) as a model and explored the mechanisms and effects that epithelial mucosa had on PCs formation and the subsequent impact on the transcellular transport of Tf-NPs. In mucus-secreting cells, Tf-NPs adsorbed more proteins from the mucus layers, which masked, displaced, and dampened the active targeting effects of Tf-NPs, thereby weakening endocytosis and transcellular transport efficiencies. In mucus-free cells, Tf-NPs adsorbed more proteins during intracellular trafficking, which enhanced transcytosis related functions. Inspired by soft coronas and artificial biomimetic membranes, we used mucin as an "active PC" to precoat Tf-NPs (M@Tf-NPs), which limited the negative impacts of "passive PCs" formed during interface with the epithelial mucosa and improved favorable routes of endocytosis. M@Tf-NPs adsorbed more proteins associated with endoplasmic reticulum-Golgi functions, prompting enhanced intracellular transport and exocytosis. In summary, mucus shielded against the absorption of Tf-NPs, but also could be employed as a spear to break through the epithelial mucosa barrier. These findings offer a theoretical foundation and design platform to enhance the efficiency of oral-administered nanomedicines.

Capecitabine-associated gastrointestinal ulceration, haemorrhage, and obstruction: a pharmacovigilance analysis based on the FAERS.

Capecitabine has been reported to be associated with severe gastrointestinal (GI) adverse drug reactions (gastrointestinal ulceration, haemorrhage, and obstruction). However, statistical correlations have not been demonstrated, and specific GI adverse drug reactions, such as GI obstruction, are not listed on its label. We aimed to determine the associations between capecitabine and GI ulceration, haemorrhage, or obstruction among patients with breast cancer by examining data from the United States Food and Drug Administration Adverse Event Reporting System (FAERS). We performed disproportionality analysis of GI ulceration, haemorrhage, and obstruction by evaluating the reporting odds ratio (ROR) and the information component (IC) with their 95% confidence intervals (CIs). We identified 279 patients with capecitabine-associated GI ulceration, haemorrhage, or obstruction reported between 1 January 2004 and 31 December 2020. One-fourth of the cases of GI ulceration, haemorrhage, or obstruction resulted in death. Capecitabine as a drug class had disproportionately high reporting rates for GI ulceration [ROR 1.94 (1.71-2.21); IC 0.80 (0.60-0.99)], haemorrhage [ROR 2.27 (1.86-2.76); IC 0.99 (0.69-1.28)], and obstruction [ROR 2.19 (1.63-2.95); IC 0.96 (0.51-1.40)]. Pharmacovigilance research on the FAERS has revealed a slight increase in reports of GI ulceration, haemorrhage, and obstruction in capecitabine users, which may cause serious or deadly consequences. In addition to the adverse reactions described in the package insert, close attention should be paid to GI obstruction to avoid discontinuation or life-threatening outcomes.

Advances in the Evaluation of Gastrointestinal Absorption Considering the Mucus Layer.

Because of the increasing sophistication of formulation technology and the increasing polymerization of compounds directed toward undruggable drug targets, the influence of the mucus layer on gastrointestinal drug absorption has received renewed attention. Therefore, understanding the complex structure of the mucus layer containing highly glycosylated glycoprotein mucins, lipids bound to the mucins, and water held by glycans interacting with each other is critical. Recent advances in cell culture and engineering techniques have led to the development of evaluation systems that closely mimic the ecological environment and have been applied to the evaluation of gastrointestinal drug absorption while considering the mucus layer. This review provides a better understanding of the mucus layer components and the gastrointestinal tract's biological defense barrier, selects an assessment system for drug absorption in the mucus layer based on evaluation objectives, and discusses the overview and features of each assessment system.

Oral Drug Absorption and Drug Disposition in Critically Ill Cardiac Patients.

(1) Background: In critically ill cardiac patients, parenteral and enteral food and drug administration routes may be used. However, it is not well known how drug absorption and metabolism are altered in this group of adult patients. Here, we analyze drug absorption and metabolism in patients after cardiogenic shock using the pharmacokinetics of therapeutically indicated esomeprazole. (2) Methods: The pharmacokinetics of esomeprazole were analyzed in a consecutive series of patients with cardiogenic shock and controls before and after elective cardiac surgery. Esomeprazole was administered orally or with a nasogastric tube and once as an intravenous infusion. (3) Results: The maximum plasma concentration and AUC of esomeprazole were, on average, only half in critically ill patients compared with controls (p < 0.005) and remained lower even seven days later. Interestingly, esomeprazole absorption was also markedly compromised on day 1 after elective surgery. The metabolites of esomeprazole showed a high variability between patients. The esomeprazole sulfone/esomeprazole ratio reflecting CYP3A4 activity was significantly lower in critically ill patients even up to day 7, and this ratio was negatively correlated with CRP values (p = 0.002). The 5'-OH-esomeprazole and 5-O-desmethyl-esomeprazol ratios reflecting CYP2C19 activity did not differ significantly between critically ill and control patients. (4) Conclusions: Gastrointestinal drug absorption can be significantly reduced in critically ill cardiac patients compared with elective patients with stable cardiovascular disease. The decrease in bioavailability indicates that, under these conditions, any vital medication should be administered intravenously to maintain high levels of medications. After shock, hepatic metabolism via the CYP3A4 enzyme may be reduced.

Association of ABCB1 Polymorphisms with Efficacy and Adverse Drug Reactions of Valproic Acid in Children with Epilepsy.

Genetic polymorphisms in ATP-binding cassette subfamily B member 1 (ABCB1, also known as MDR1) have been reported to be possibly associated with the regulation of response to antiseizure medications. The aim of this study was to investigate the association of ABCB1 polymorphisms with the efficacy of and adverse drug reactions to valproic acid among Chinese children with epilepsy. A total of 170 children from southern China with epilepsy treated with valproic acid for more than one year were recruited, including 61 patients with persistent seizures and 109 patients who were seizure-free. Two single nucleotide polymorphisms of ABCB1, rs1128503 and rs3789243, were genotyped using the Sequenom MassArray system. The two single nucleotide polymorphisms of ABCB1 were found to be significantly associated with treatment outcomes of valproic acid in children with epilepsy. Carriers with the TT genotype of ABCB1 rs1128503 were more inclined to exhibit persistent seizures after treatment with valproic acid (p = 0.013). The CC genotype of rs3789243 was observed to be a potential protective factor for valproic acid-induced gastrointestinal adverse drug reactions (p = 0.018), but possibly increased the risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). In contrast, the CT genotype of rs3789243 was associated with a lower risk of valproic acid-induced cutaneous adverse drug reactions (p = 0.011). Haplotype analysis showed that CC haplotype carriers tended to respond better to valproic acid treatment (p = 0.009). Additionally, no significant association was found between ABCB1 polymorphisms and serum concentrations of valproic acid. This study revealed that the polymorphisms and haplotypes of the ABCB1 gene might be associated with the treatment outcomes of valproic acid in Chinese children with epilepsy.

Effect of intragranular/extragranular tara gum on sustained gastrointestinal drug delivery from semi-IPN hydrogel matrices

The present research was undertaken to develop semi-IPN hydrogel matrix tablets of tara gum (TG) and carboxymethyl TG (CMTG) for sustained gastrointestinal delivery of highly water soluble tramadol hydrochloride (TH). The matrix tablets were developed by a hybrid process of wet granulation and direct compression technique. Carboxymethyl TG was crosslinked with dual cross-linking ions (Al3+/Ca2+). The uncross-linked component of the semi-IPN matrix was either incorporated within the granules (intragranular TG) or incorporated outside the granules (extragranular TG), prior to compression. The effect of intragranular/extragranular TG on the swelling, erosion and TH release characteristics from the semi-IPN hydrogel matrix tablets was investigated. The key finding of the investigation indicated that intragranular TG expedited TH release, while extragranular TG sustained TH release. Moreover, the effect of cross-linking ions on viscosity, rigidity, cross-link density and TH release behavior from hydrogel matrices was investigated. In-vivo pharmacokinetic performance of the optimized extragranular TG semi-IPN hydrogel matrix (F15) indicated sustained TH release in gastrointestinal milieu.

Development of an In Vitro Methodology to Assess the Bioequivalence of Orally Disintegrating Tablets Taken without Water.

To assess the probability of bioequivalence (BE) between orally disintegrating tablets (ODTs) taken without water and conventional tablets (CTs) taken with water, an in vitro biorelevant methodology was developed using the BE Checker, which reproduces fluid shifts in the gastrointestinal tract and drug permeation. In addition to the fluid shift from the stomach to the small intestine, the process of ODT disintegration in a small amount of fluid in the oral cavity and the difference in gastric emptying caused by differences in water intake were incorporated into the evaluation protocol. Assuming a longer time to maximum plasma concentration after oral administration of ODTs taken without water than for CTs taken with water due to a delay in gastric emptying, the fluid shift in the donor chamber of the BE Checker without water was set longer than that taken with water. In the case of naftopidil ODTs and CTs, the values of the f2 function, representing the similarity of the permeation profiles, were 50 or higher when the fluid shift in ODTs taken without water was set at 1.5 or 2 times longer than that of the CTs taken with water. The values of the f2 function in permeation profiles of pitavastatin and memantine ODTs were both 62 when the optimized experimental settings for naftopidil formulations were applied. This methodology can be useful in formulation studies for estimating the BE probability between ODTs and CTs.

Formulation and Characterization of a New Gastrointestinal Drug Delivery System of Cinnarizine Hydrochloride

The goal of this study was to create and test an in vitro floating drug delivery system employing polymers such as sodium carboxymethyl cellulose (CMC Sodium), Xanthan gum (XG), and sodium alginate (SA), using cinnarizine hydrochloride (CNZ) as the model drug. The efficacy of the model drug was proven during the pre-formulation research. 18 distinct formulations were developed using a direct compression (effervescent) technique (F1-F18). As a gas generator, sodium bicarbonate was employed. Physical properties such as weight variation, hardness, friability, floating lag time, and total floating duration were assessed in all of the formulations. Four mathematical models were used to predict the drug release Kinetics: zero order, first order, Higuchi, and Korsmeyer Peppas. F1, F2, F3, F6, and F7 were known to be the optimum formulations. They all include the same amount of sodium bicarbonate (40 mg) and ethyl cellulose (40 mg), but different quantities of CMC Sodium, XG, and SA (150mg, 120mg, 90mg, 150mg and 120mg of CMC Sodium:30mg, 60mg, 90mg, 0mg, 0mg of XA &amp; 0mg, 0mg, 0mg, 30mg and 60mg of SA respectively). In 0.1N HCl, all of the optimized batches had a release rate of 92 % to 99.8% in 12 hours and showed adequate swelling for up to 10 hours. Polymers such as CMC sodium, XG, and SA, in conjunction with sodium bicarbonate as a gas producing agent, may be employed to formulate sustained release floating tablets containing CNZ, according to the findings.