Quality by Design Approach for Optimization of Microbial and pH-Triggered Colon-Targeted Tablet Formulation Using Carboxymethyl Tamarind Gum.

ABSTRACT The purpose of this study was to apply the quality by design (QbD) approach in the development of a microbial and pH-triggered colon-targeted budesonide tablet. A retrospective research strategy was used to select various polysaccharide-based natural gums such as tamarind gum, gellan gum, karaya gum, gum ghutti, and khaya gum, which were then evaluated for their effectiveness in microbial degradation and targeting the colon. Viscosity profiles were generated in the presence of a prebiotic culture medium prepared by using the Velgut capsule that mimicked the impact of 4% rat cecal content and helpful in screening of natural polymer. Based on the cumulative drug release data of preliminary batches, carboxymethyl (CM) tamarind gum was identified as a superior and an excellent polymer over the tamarind gum for formulation development. The presence of water as a bridging agent in wet granulation also played an important role in the retardation of drug release. Tablets were supercoated with the enteric polymer, Eudragit S100. The Box-Behnken design was utilized, where the selected independent variables were the proportion of CM tamarind gum, % water proportion, and % weight gain of Eudragit S 100 to optimize the formulation. The optimized design space was generated with the criteria that a drug release should be of less than 5% within the first 2 h, less than 10% within the first 5 h, and more than 70% within the first 8 h, to achieve colon targeting. The optimized batch F3 was found stable as per International Council for Harmonisation guidelines. The roentgenography study for optimized formulation demonstrated that it remained intact for 5 h and, at 7 h, was disseminated completely. CM tamarind gum is efficient for colon targeting, and its proportion in 100 mg along with an enteric coating of 6% led to the optimized formulation.

Film Coatings Based on Aqueous Shellac Ammonium Salt "Swanlac® ASL 10" and Inulin for Colon Targeting.

Over the past decades, increasing interests took place in the realm of drug delivery systems. Beyond treating intestinal diseases such as inflammatory bowel disease, colon targeting can provide possible applications for oral administration of proteins as well as vaccines due to the lower enzymatic activity in the distal part of GIT. To date, many strategies are employed to reach the colon. This article encompasses different biomaterials tested as film coatings and highlights appropriate formulations for colonic drug delivery. A comparison of different films was made to display the most interesting drug release profiles. These films contained ethylcellulose, as a thermoplastic polymer, blended with an aqueous shellac ammonium salt solution. Different blend ratios were selected as well for thin films as for coated mini-tablets, mainly varying as follows: (80:20); (75:25); (60:40). The impact of blend ratio and coating level was examined as well as the addition of natural polysaccharide "inulin" to target the colon. In vitro drug release was measured in 0.1 M HCl for 2 h followed by phosphate buffer saline pH 6.8 to simulate gastric and intestinal fluids, respectively. Coated mini-tablets were exposed to fresh fecal samples of humans in order to simulate roughly colonic content. Several formulations were able to fully protect theophylline as a model drug up to 8 h in the upper GIT, but allowing for prolonged release kinetics in the colon. These very interesting colonic release profiles were related to the amount of the natural polysaccharide added into the system.

Boosting systemic absorption of peptides with a bioinspired buccal-stretching patch.

Biopharmaceuticals, including proteins and peptides, have revolutionized the treatment of a wide range of diseases, from diabetes and cardiovascular disorders to virus infections and cancer. Despite their efficacy, most of these macromolecular drugs require parenteral administration because of their high molecular weight and relative instability. Over the past 40 years, only a few oral peptide drugs have entered clinical trials, even when formulated with substantial amounts of permeation enhancers. To overcome the epithelial barrier, devices that inject drugs directly into the gastrointestinal mucosa have been proposed recently. However, the robustness and safety of those complex systems are yet to be assessed. In this study, we introduced an innovative technology to boost drug absorption by synergistically combining noninvasive stretching of the buccal mucosa with permeation enhancers. Inspired by the unique structural features of octopus suckers, a self-applicable suction patch was engineered, enabling strong adhesion to and effective mechanical deformation of the mucosal tissue. In dogs, this suction patch achieved bioavailability up to two orders of magnitude higher than those of the commercial tablet formulation of desmopressin, a peptide drug known for its poor oral absorption. Moreover, systemic exposure comparable to that of the approved oral semaglutide tablet was achieved without further optimization. Last, a first-in-human study involving 40 healthy participants confirmed the dosage form's acceptability, thereby supporting the clinical translatability of this simple yet effective platform technology.

Development of a time-dependent oral colon delivery system of anaerobic Odoribacter splanchnicus for bacteriotherapy.

Odoribacter (O.) splanchnicus is an anaerobic member of the human intestinal microbiota. Its decrease in abundance has been associated with inflammatory bowel disease (IBD), non-alcoholic fatty liver, and cystic fibrosis. Considering the anti-inflammatory properties of O. splanchnicus and its possible use for IBD, intestinal isolate O. splanchnicus 57 was here formulated for oral colonic release based on a time-dependent strategy. Freeze-drying protocol was determined to ensure O. splanchnicus 57 viability during the process. Disintegrating tablets, containing the freeze-dried O. splanchnicus 57, were manufactured by direct compression and coated by powder-layering technique with hydroxypropyl methylcellulose (Methocel™ E50) in a tangential-spray fluid bed. Eudragit® L was then applied by spray-coating in a top-spray fluid bed. Double-coated tablets were tested for release, showing gastric resistance properties and, as desired, lag phases of reproducible duration prior to release in phosphate buffer pH 6.8. The cell viability and anti-inflammatory activity of the strain were assessed after the main manufacturing steps. While freeze-drying did not affect bacterial viability, the tableting and coating processes were more stressful. Nonetheless, O. splanchnicus 57 cells survived manufacturing and the final formulations had 106-107 CFU/g of viable cells. The strain kept its anti-inflammatory properties after tableting and coating, reducing Escherichia coli lipopolysaccharide-induced interleukin-8 cytokine release from HT-29 cells. Overall, O. splanchnicus 57 strain was formulated successfully for oral colon delivery, opening new ways to formulate pure cultures of single anaerobic strains or mixtures for oral delivery.

Form & formulation approaches for COntRollable Release in 3D printed Colonic Targeting (CORR3CT) budesonide tablet.

Inflammatory bowel disease (IBD) represents a group of chronic and debilitating inflammatory diseases affecting various parts of the gastrointestinal (GI) tract. The disease incidence and prevalence have been growing worldwide since the early 21st century and this upward trend is expected to continue. Due to a complex and variable clinical presentation across different patients, the efficacy of a one-size-fits-all commercial formulation for IBD remains limited. Here, we present the development of a novel adjustable and controllable release, 3D printed colonic targeting (CORR3CT) dosage form of budesonide, to reduce off-targeting adverse effects and to potentially replace the use of enemas, which are invasive and commonly associated with poor adherence. An in vitro Gastrointestinal Simulated System (GISS) model was employed in this study to examine the ability of the 3D printed tablets to deliver budesonide to various targeted sites along the gastrointestinal tract. CORR3CT tablet with Pill-in-pill configurations were designed, fabricated and the relationship between the 3D printed design and resultant dissolution profiles were established. The 3D printed tablets also exhibited excellent and comparable dose accuracy and quality versus commercial tablets, while enhancing the delivery of budesonide to the targeted colon region. Overall, this study has laid the foundational proof of concept demonstrating controllable targeting of oral therapeutics along the gastrointestinal tract using 3D printing technologies.

Tablet formulation with dual control concept for efficient colonic drug delivery.

Aim of this study was to develop a tablet formulation for targeted colonic drug release by implementing two control mechanisms: A pH-sensitive coating layer based on Eudragit® FS 30 D to prevent drug release in the upper gastrointestinal tract, combined with a matrix based on plant-derived polysaccharide xyloglucan to inhibit drug release after coating removal in the small intestine and to allow microbiome triggered drug release in the colon. In vitro dissolution tests simulated the passage through the entire gastrointestinal tract with a four-stage protocol, including microbial xyloglucanase addition in physiologically relevant concentrations as microbiome surrogate to the colonic dissolution medium. Matrix erosion was monitored in parallel to drug release by measurement of reducing sugar equivalents resulting from xyloglucan hydrolysis. Limited drug release in gastric and small intestinal test stages and predominant release in the colonic stage was achieved. The xyloglucan matrix controlled drug release after dissolution of the enteric coating through the formation of a gummy polysaccharide layer at the tablet surface. Matrix degradation was dependent on enzyme concentration in the colonic medium and significantly accelerated drug release resulting in erosion-controlled release process. Drug release at physiologically relevant enzyme concentration was completed within the bounds of colonic transit time. The dual control concept was applicable to two drug substances with different solubility, providing similar release rates in colonic environment containing xyloglucanase. Drug solubility mechanistically affected release, with diffusion of caffeine, but not of 5-ASA, contributing to the overall release rate out of the matrix tablet.

Neurotransmitter transporter occupancy following administration of centanafadine sustained-release tablets: A phase 1 study in healthy male adults.

BACKGROUND: Centanafadine is an inhibitor of reuptake transporters for norepinephrine (NET), dopamine (DAT) and serotonin (SERT). AIMS: This phase 1, adaptive-design positron emission tomography study investigated the occupancy time course of NET, DAT, and SERT and the relationship to centanafadine plasma concentrations. METHODS: Healthy adult males received centanafadine sustained-release 400 mg/day for 4 days (N = 6) or 800 mg in a single day (N = 4). Assessments included safety monitoring; time course of occupancy of NET, DAT, and SERT; and centanafadine plasma concentrations. RESULTS: Transporter occupancy was numerically higher for NET versus DAT or SERT. For NET, estimated (mean ± standard error [SE]) maximal observable target occupancy (TOmax) and concentration at half maximal occupancy (IC50) were 64 ± 7% and 132 ± 65 ng/mL, respectively, for all regions and 82 ± 13% and 135 ± 97 ng/mL after excluding the thalamus, which showed high nonspecific binding. For DAT and SERT, TOmax could not be established and was assumed to be 100%; estimated IC50 (mean ± SE) values were 1580 ± 186 ng/mL and 1,760 ± 309 ng/mL, respectively. For centanafadine, the estimated in vivo affinity ratio was 11.9 ± 6.0 (mean ± SE) for NET/DAT, 13.3 ± 7.0 for NET/SERT, and 1.1 ± 0.2 for DAT/SERT. DAT and SERT occupancies at a plasma concentration of 1400 ng/mL were estimated to be 47 and 44%, respectively. CONCLUSIONS: High occupancy at NET and moderate occupancy at DAT and SERT was observed at peak concentrations achieved following 400 mg total daily doses of centanafadine.

Metabonomic and transcriptomic analyses of Tripterygium glycosides tablet-induced hepatotoxicity in rats.

We aimed to explore novel biomarkers involved in alterations of metabolism and gene expression related to the hepatotoxic effects of Tripterygium glycosides tablet (TGT) in rats. Rats were randomly divided into groups based on oral administration of TGTs for 6 weeks: control, low-dose (9.5 mg/kg), and high-dose (18.9 mg/kg). Serum samples and total liver RNA were subjected to metabonomic and transcriptomic analyses. Thirteen metabolites were significantly up-regulated by liver injury induced by Tripterygium glycosides. Five potential biomarkers were more sensitive than Alanine aminotransferase (ALT) for accurate and timely prediction of hepatic damage. The four metabolic pathways most obviously regulated by hepatotoxicity were D-glutamine and D-glutamate metabolism, alanine, aspartate and glutamate metabolism, ether lipid metabolism, and tryptophan metabolism. Transcriptomics revealed significant differences in 1792 mRNAs and 400 long non-coding (lnc) RNAs. Dysregulated lncRNAs in the TGT-induced hepatotoxicity group were associated with genes involved in amino acid metabolism using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis. Up-regulated expression of Ehhadh, Gpt, and Got1, and down-regulated expression of dopa decarboxylase (Ddc), Cyp1a2, Ido2, Aldh1b1, and asparagine synthetase (Asns) was validated by quantitative real-time PCR. This multiomics study has elucidated the relationship between amino metabolism and liver injury, revealing potential biomarkers.

Tripterygium glycoside tablet attenuates renal function impairment in diabetic nephropathy mice by regulating triglyceride metabolism.

Tripterygium glycoside tablet (TGT) has been used clinically to alleviate diabetic nephropathy (DN) for decades. However, the mechanism of its anti-DN has not been fully clarified. The aim of this study was to elucidate molecular mechanism of TGT in repairing renal function injury. The results of biochemical parameters and renal histopathology implied that TGT intervention could attenuate creatinine, albumin excretion rate and histological injury of kidney in DN mouse model. Moreover, UHPLC-QTOF-MS/MS-based untargeted metabolomic analysis indicated that 11 metabolites in kidney of mice with DN were restored after TGT treatment, and the most prominent metabolic alteration was triglyceride (TG) metabolism. Mechanistically, TGT effectively improved the function of impaired kidney by promoting TG catabolism via modulation of adipose triglyceride lipase in DN mice. Our findings identified the link between circulating metabolites and DN, suggesting that it might be a possibility to intervene in DN by targeting metabolism.

Clinical Effect of Metronidazole Vaginal Effervescent Tablet Combined with Flavescentis Sophora Suppository in the Treatment of Trichomonas Vaginitis.

For the treatment of trichomonas vaginitis, a combination therapy of metronidazole vaginal effervescent tablet combined with Flavescentis Sophora suppository is proposed. The patients diagnosed with trichomonas vaginitis are divided into the conventional treatment group and the joint group. The conventional group is treated with metronidazole vaginal effervescent tablets, and the joint group is treated with metronidazole vaginal effervescent tablets combined with sophora bolt. Both groups are treated for 3 months to observe the therapeutic effect of the two treatment methods. The expressions of IL-2 and IL-13 in serum of patients are detected by the ELISA. The changes in the vaginal pH value and cleanliness at each time point are observed. The patients are followed up for 6 months after treatment in order to observe the recurrence of trichomonas vaginitis in both groups. Experimental results show that the combination of the two tablets can further improve the clinical efficacy and reduce the inflammatory response and effectively improve the PH value and cleanliness of the vagina, and the recurrence rate is lower, which is worthy of clinical application.

Effects of ginkgo leaf tablet on the pharmacokinetics of rosiglitazone in rats and its potential mechanism.

CONTEXT: Ginkgo leaf tablet (GLT), a traditional Chinese herbal formula, is often combined with rosiglitazone (ROS) for type 2 diabetes mellitus treatment. However, the drug-drug interaction between GLT and ROS remains unknown. OBJECTIVE: To investigate the effects of GLT on the pharmacokinetics of ROS and its potential mechanism. MATERIALS AND METHODS: The pharmacokinetics of 10 mg/kg ROS with 100/200 mg/kg GLT as single-dose and 10-day multiple-dose administration were investigated in Sprague-Dawley rats. In vitro, the effects of GLT on the activity of CYP2C8 and CYP2C9 were determined in recombinant human yeast microsomes and rat liver microsomes with probe substrates. RESULTS: The t1/2 of ROS increased from 2.14 ± 0.38 (control) to 2.79 ± 0.37 (100 mg/kg) and 3.26 ± 1.08 h (200 mg/kg) in the single-dose GLT administration. The AUC0-t (139.69 ± 45.46 vs. 84.58 ± 39.87 vs. 66.60 ± 15.90 h·µg/mL) and t1/2 (2.75 ± 0.70 vs. 1.99 ± 0.44 vs. 1.68 ± 0.35 h) decreased significantly after multiple-dose GLT treatment. The IC50 values of quercetin, kaempferol, and isorhamnetin, GLT main constituents, were 9.32, 7.67, and 11.90 µmol/L for CYP2C8, and 27.31, 7.57, and 4.59 µmol/L for CYP2C9. The multiple-dose GLT increased rat CYP2C8 activity by 44% and 88%, respectively. DISCUSSION AND CONCLUSIONS: The metabolism of ROS is attenuated in the single dose of GLT by inhibiting CYP2C8 and CYP2C9 activity, and accelerated after the multiple-dose GLT treatment via inducing CYP2C8 activity in rats, indicating that the clinical dose of ROS should be adjusted when co-administrated with GLT.

Qiangjing tablets repair of blood-testis barrier dysfunction in rats via regulating oxidative stress and p38 MAPK pathway.

BACKGROUND: The blood-testis barrier (BTB) is a physical barrier of the testis to prevent various exogenous substrates from entering apical compartments and provides immune privilege for spermatogenesis, which is essential for normal spermatogenic function of testis. It has been shown that oxidative stress can damage BTB by activating the p38 MAPK pathway. In Traditional Chinese Medicine, Qiangjing tablets (QJT) improve spermatogenesis and increase pregnancy rates. Previous studies have confirmed that QJT can improve sperm quality and have obvious antioxidant effects. In this study, we explore whether QJT contributes to recovery from BTB dysfunction in rats. METHODS: BTB dysfunction was induced in rats by 1% Cyclophosphamide (CP). The CP-induced rats in the treatment group were given a dose of QJT (0.45 g/kg·d) by gavage. Testis tissues were collected for histopathological and biochemical analysis, and the testis weight was estimated. Levels of BTB-related proteins and antioxidant enzyme were analyzed in the testis tissues. RESULTS: QJT resolved the pathological injury of rats testis induced by CP. Furthermore, MDA levels were significantly reduced, and the levels of SOD markedly increased in the testicular tissue after QJT treatment. In addition, QJT down-regulated the expression of p38 protein in rat testis and up-regulated the expressions of key proteins ZO-1, occludin and F-actin in BTB. CONCLUSION: These results demonstrate that QJT exerts protective effects on CP-induced rats with BTB dysfunction, likely by regulating the oxidative stress-mediated p38 MAPK pathway.

Prediction of quality attributes (mechanical strength, disintegration behavior and drug release) of tablets on the basis of characteristics of granules prepared by high shear wet granulation.

High shear wet granulation is commonly applied technique for commercial manufacturing of tablets. Granulation process for tablets manufacturing is generally optimized by hit and trial which involves preparation of granules under different processing parameters, compression of granules and evaluation of the resultant tablets; and adjustment is made in granulation process on the basis of characteristics of tablets. Objective of the study was to optimize the process of high shear wet granulation and prediction of characteristics of tablets on the basis of properties of granules. Atenolol granules were prepared by high shear wet granulation method, using aqueous solution of polyvinyl pyrrolidone (PVP k-30) as binder. Concentration of binder solution and granulation time were taken as process variables, both studied at three levels. Different combinations of process variables were determined by Design Expert software. Granules were evaluated for different parameters on the basis of SeDeM-ODT (Sediment Delivery Model-Oro Dispersible Tablets) expert system. Granules from all the trials were compressed using round (10.5 mm) flat faced punches at compression weight of 250 mg/tablet. Tablets were evaluated of different quality control parameters as per USP. Results showed that both the process variables had positive effect on mechanical strength of tablets and negative effect on disintegration and dissolution rate. Granule prepared with highest level of binder concentration (15%) and highest granulation time (60 sec) resulted in tablets with highest crushing strength (11.8 kg), specific crushing strength (0.328 kg/mm2), tensile strength (0.208 kg/mm2), lowest value of friability (0.19%) and highest disintegration time (10.9 min), as predicted from granules characteristics on the basis of SeDeM-ODT expert system. Drug release from Trial-13 (processed under highest level of both process parameters) was also lower than rest of the trials. It is concluded from the study that quality characteristics of tablets can be predicted from granules characteristics using SeDeM-ODT expert system. Furthermore, SeDeM-ODT expert system can also be used for optimization of the process of high shear wet granulation.

The Efficacy of Hydroxychloroquine Combined with Huangqi Tablets in the Treatment of Diabetic Nephropathy.

Objective: This study aimed to analyze the effect of hydroxychloroquine combined with Huangqi tablets in the treatment of diabetic nephropathy (DN). Methods: Eighty patients with DN were enrolled and divided into two groups by a random number table. 27 patients received routine treatment + hydroxychloroquine (group A), while 27 patients received routine treatment + hydroxychloroquine + Huangqi tablets (group B) and 26 patients received routine treatment (group C). Results: FPG, 2h PG, and HbA1c levels as well as TC and TG levels were lower in group B than in groups A and C at the end of 3 months of treatment and were lower in group A than in group C (P < 0.05). SCR, BUN, and 24-hour urine protein were reduced in group B after therapy, whereas eGFR was increased and the difference between groups A and C was significant (P=0.05). After treatment, VEGF, IGF-1, and TGF-1 levels were lower in group B than in groups A and C and in group A than in group C (P=0.05). Total symptom scores at 2, 4, and 6 months after treatment was lower in group B than in groups A and C, and they were lower in group A than in group C at all time points (P < 0.05). The total effective rates of treatment in groups A, B, and C were 66.67%, 88.89%, and 38.46% (P < 0.05). The incidence of adverse reactions in groups A, B, and C was 37.04%, 25.93%, and 11.54% (P > 0.05). Conclusion: Hydroxychloroquine combined with Huangqi tablets in the treatment of DN showed the best efficacy, with better control of blood glucose and lipids, which can more effectively delay the progression of renal lesions and effectively inhibit the expression of VEGF, IGF, and TGF-ß1 in tethered cells with high safety.

Influence of chitosan thioglycolic acid conjugate in improving bioavailability of an antiparkinson drug; Rasagiline Mesylate from transdermal patch.

OBJECTIVE: Parkinson disease (PD) is a chronic disorder of central nervous system mainly affecting the motor systems. The drug of choice to treat PD is Rasagiline Mesylate (RM) and it belongs to BCS class III drug. The objective of the present study was the preparation of transdermal drug delivery system for RM. Several permeation enhancers were screened to be included in the formulation. To achieve desired flux a new strategy was developed by including in-house prepared CTC to enhance the permeation of RM. METHODS: The CTC was prepared by reaction between chitosan and thioglycolicacid, characterized by determining physical properties and applying analytical tools. Seven permeation enhancers with different mechanisms were screened. The transdermal patches were prepared with chitosan along with permeation enhancer IPM, various proportions of CTC and evaluated for physical and permeation studies. The optimized transdermal patch was obtained by two factors and three responses to obtain the design space and further evaluated for pharmacokinetic studies. RESULTS: The results of the present study confirmed the formation of CTC, IPM was best permeation enhancer among all. The presence of CTC in the formulations significantly improved the permeation of RM to achieve desired steady-state flux. The relative bioavailability of optimized transdermal patch was determined and it was observed that improved bioavailability as compared to marketed conventional tablets. CONCLUSION: The study was concluded that CTC has significant influence on permeation enhancing ability of IPM.

Studying Drug Release through Polymeric Controlled Release Formulations in United States Pharmacopoeia 2 Apparatus Using Multiphysics Simulation and Experiments.

In vitro dissolution of oral drug formulations is often studied using the United States Pharmacopoeia (USP) apparatus. Although a well-stirred vessel or a perfect sink assumption is often employed in the modeling of in vitro dissolution in USP apparatus, such a limit is usually not realized in actual experimental conditions. The interplay of hydrodynamics in the vessel and the swelling and erosion of dosage forms often results in substantial deviations from the dissolution behavior obtained under perfect sink approximation. We develop a multiphysics model of drug release from controlled release tablets of polymeric excipients with active pharmaceutical ingredients (APIs). Simulations are performed in COMSOL for the USP 2 (paddle) apparatus and the effects of stirring speed, drug loading, erosion rate, and polymer swelling and erosion are analyzed in detail. We demonstrate that the drug release phenomena can be conveniently interpreted using the Weibull equation to fit the simulation results. This is further confirmed using drug release experiments performed on mechanically compressed tablets of naproxen sodium as the API with poly-methyl-methacrylate-co-methacrylic acid as the excipient. We show that the API-to-polymer ratio may be varied to obtain different regimes of controlled release.

Evaluating the Impact of Physiological Properties of the Gastrointestinal Tract On Drug In Vivo Performance Using Physiologically Based Biopharmaceutics Modeling and Virtual Clinical Trials.

The physiological properties of the gastrointestinal tract, such as pH, fluid volume, bile salt concentration, and gastrointestinal transit time, are highly variable in vivo. These properties can affect the dissolution and absorption of a drug, depending on its properties and formulation. The effect of gastrointestinal physiology on the bioperformance of a drug was studied in silico for a delayed-release pantoprazole tablet and an immediate-release dolutegravir tablet. Physiologically based absorption models were developed and virtual clinical trials were performed. Reasons for the variability in drug bioperformance between subjects were investigated, taking into account differences in gastrointestinal tract characteristics, pharmacokinetic parameters, and additional parameters (e.g., permeability). Default software parameters describing gastrointestinal physiology in the fasted and fed states, and variation in these parameters, were altered to match variability in these parameters reported in vivo. The altered model physiologies better described the variability of gastrointestinal conditions, and therefore the results of virtual trials using these physiologies are likely to be more relevant in vivo. With such altered gastrointestinal physiologies used to develop models, it is possible to obtain additional knowledge and improve the understanding of subject-formulation interactions.

Formulation and Quality Control of Orally Disintegrating Tablets (ODTs): Recent Advances and Perspectives.

Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown in the pharmaceutical industry and academia. It is reported that ODTs have several advantages over other conventional tablets. Since some of them are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach, in such cases, the bioavailability of the drug improves meaningfully. Furthermore, the immediate release property of ODTs makes them a popular oral dosage form in patients with swallowing challenges, children, and for cases with a need for rapid onset of action. The current review article explains the features of active ingredients and excipients used in the formulation of ODTs, discusses multiple ODT formulation and preparation techniques with their merits and demerits, and also, offers remedies for problems associated with ODTs. Moreover, quality control steps and required considerations are presented.

The preparation and validation of chitosan tablets that rapidly disperse and disintegrate as an oral adsorbent in the treatment of lifestyle-related diseases.

A carrier and an oral absorbent for the treatment of chronic diseases in the form of a tablet was prepared from granulated chitosan (G-CS) particles. The resulting tablet was highly dispersible and disintegrated rapidly (< 30 s) in aqueous media. The non-granulated chitosan (N-CS) powder partially crystallized (2θ = 12-15° and 20°) during wet granulation to give G-CS crystalline particles. The rate of penetration of water into G-CS aggregates was markedly faster than that for N-CS aggregates, as evidenced by the ease of disintegration of the tablets. The rapid disintegration and dispersion of the tablets in vivo was confirmed by MRI measurements after the oral administration of the both tablets to rats. Some ureic toxins were adsorbed more strongly to G-CS tablets than on N-CS tablets. The results suggest that G-CS tablets have great potential for use as a fast disintegrating carrier and as an oral adsorbent in lifestyle-related diseases.

IVIVC for Extended Release Hydrophilic Matrix Tablets in Consideration of Biorelevant Mechanical Stress.

PURPOSE: When establishing IVIVC, a special problem arises by interpretation of averaged in vivo profiles insight of considerable individual variations in term of time and number of mechanical stress events in GI-tract. The objective of the study was to investigate and forecast the effect of mechanical stress on in vivo behavior in human of hydrophilic matrix tablets. METHODS: Dissolution profiles for the marketed products were obtained at different conditions (stirring speed, single- or repeatable mechanical stress applied) and convoluted into C-t profiles. Vice versa, published in vivo C-t profiles of the products were deconvoluted into absorption profiles and compared with dissolution profiles by similarity factor. RESULTS: Investigated hydrophilic matrix tablets varied in term of their resistance against hydrodynamic stress or single stress during the dissolution. Different scenarios, including repeatable mechanical stress, were investigated on mostly prone Seroquel® XR 50 mg. None of the particular scenarios fits to the published in vivo C-t profile of Seroquel® XR 50 mg representing, however, the average of individual profiles related to scenarios differing by number, frequency and time of contraction stress. When different scenarios were combined in different proportions, the profiles became closer to the original in vivo profile including a burst between 4 and 5 h, probably, due to stress-events in GI-tract. CONCLUSION: For establishing IVIVC of oral dosage forms susceptible mechanical stress, a comparison of the deconvoluted individual in vivo profiles with in vitro profiles of different dissolution scenarios can be recommended.