The effectiveness of split tablet dosing versus alternate-day dosing of warfarin: a randomized control trial.

Due to large dosage variation, a variety of warfarin prescription regimens are utilized for specific doses such as tablet splitting, or pill strength alternating. The clinical comparison between the two is lacking. We hypothesize that both approaches result in different times in therapeutic range. We randomized patients with specific warfarin dosage and stable INR for 6 months or longer to receive the whole tablet, alternate-day dosing or the split tablet, same daily-dosing regimen without initial dose change and followed them every 6 weeks for 6 months. The primary outcome was a time in therapeutic range of 2.0-3.0. The secondary outcomes included dosage, compliance, INR, anticoagulant-related events. A total of 66 patients were enrolled, 32 randomly assigned to the split tablet regimen (group S) and 34 to the alternate-day regimen (group A) with two withdrawers. The mean age was 58.6 ± 8.5 years. All baseline characteristics of both groups were similar. The average time in therapeutic range was 72.8 ± 25.4% in group S and 74.9 ± 22.0% in group A (p = 0.72). There were no significant differences in warfarin dosage, compliance, INR and, complications between the two groups. Both warfarin prescription methods, the split tablet and the alternate-day had comparable time in the therapeutic range.

Uterine fibroids treatment: do we have new valid alternative? Experiencing the combination of vitamin D plus epigallocatechin gallate in childbearing age affected women.

OBJECTIVE: Uterine myomas are the most common benign tumors in females, and at least 25% of affected patients experience symptoms severe enough to need treatment, like heavy hemorrhage, pelvic pain, and infertility. Currently, a non-invasive approach is preferred in women of childbearing age who desire pregnancy. The aim of our study was to determine the effect of oral supplementation with a combination of vitamin D plus epigallocatechin gallate (EGCG) and vitamin B6 in women with myomas. PATIENTS AND METHODS: Between April and December 2020, we enrolled 95 women of childbearing age, afferent to our hospital, displaying at least one myoma with a diameter <4 cm. Patients were divided in two groups: 41 women were treated daily with two tablets of 25 µg vitamin D + 150 mg EGCG + 5 mg vitamin B6 for 4 months; 54 women, representing the control group, received no treatment. Total volume and vascularization of myomas were analyzed ultrasonographically. Bleeding and pelvic pain was also evaluated, as well as patients' quality of life and health through questionnaire Short Form Health Survey (SF-36) and Patient Global Impression of improvement (PGI-I). RESULTS: After treatment myomas' total volume and peripherical vascularization significantly decreased respectively by 37.9% (p<0.001) and 7.7%. On the other hand, we observed an increase in myomas' volume by 5.5 % and of peripherical vascularization by 5% in the control group. The treated group reported an improvement in SF-36 (p<0.001) and PGI-I (85.4%) questionnaire scores. CONCLUSIONS: We demonstrated, in young women who want to preserve fertility, that the combined supplementation of vitamin D, EGCG, and vitamin B6 reduced myomas' volume and improved patients' quality of life, without side effects.

Vaginal tablets of dequalinium chloride 10 mg versus clotrimazole 100 mg for vaginal candidiasis: a double-blind, randomized study.

PURPOSE: To compare the clinical response, microscopic examination and fungal culture between dequalinium chloride (DQC) and clotrimazole (CT) for treating vaginal candidiasis (VC). METHODS: The double-blind, randomized study was conducted from September 2014 to September 2016 at Siriraj Hospital, Thailand. Eligible participants were Thai women diagnosed with VC by microscopic examination. The exclusion criteria included immunocompromised conditions, consumption of antifungal drugs, and having recurrent VC. Each participant was randomized with a 1:1 allocation to receive six vaginal tablets of 100 mg CT or 10 mg DQC. Two visits included 10 ± 2 days (C1) and 38 ± 4 days (C2). Outcome measures were improvement of VC symptoms, microscopic examination, culture, satisfaction and tolerability. RESULTS: Of 155 eligible participants, 150 were randomized and allocated into CT (N = 76) and DQC (N = 74). The average age was 31.1 ± 7.2 years. Comparable improvement of clinical response was demonstrated (OR at C1 0.79, 95% CI 0.56-1.10, p = 0.197; and OR at C2 0.99, 95% CI 0.69-1.43, p = 0.985). Of CT and DQC groups, the microscopic examination was positive at 11/75 (14.9%) vs 18/72 (25.3%) at C1 and 18/74 (24.3%) vs 28/66 (42.4%) at C2. And the culture was positive at 25/75 (33.8%) vs 46/72 (65.7%) at C1 and at 26/74 (36.6%) vs 46/66 (69.7%) at C2. Most participants had high satisfaction and tolerability and none reported any side effects. CONCLUSION: DQC and CT show comparable clinical response but CT results in greater improvement of microscopic examination and fungal culture. CLINICAL TRIAL REGISTRATION: The Clinical Trial Registry number was NCT02242695. (September 17, 2014).

Comparative health risk assessment of realgar and NiuHuangJieDu tablets based on tissue arsenic levels after multiple oral administration to rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Realgar (As2S2), a mineral traditional Chinese medicine (TCM), is proved to have great therapeutic effects in clinic and has been widely used in China for hundreds of years. As one of the most popular realgar-containing TCMs, NiuHuangJieDu Tablets (NHJDT) is used as OTC (over-the-counter) drug in daily life for fever relieving, detoxicating, as well as cure of sore throat and gingival swelling. However, the safety of realgar and its-containing TCMs still remains unclear. AIM OF THE STUDY: This study was to investigate the accumulation of arsenic in rat body and evaluate the safety of realgar-containing TCMs in vivo. MATERIALS AND METHODS: The health risk of arsenic was evaluated in rats by tissue distribution and histopathology, as well as arsenic speciation in plasma after multiple oral gavage of low and high doses of realgar and NiuHuangJieDu Tablets (NHJDT), respectively. Total arsenic and arsenic speciation were determined by hydride generation-atomic fluorescence spectrometry (HG-AFS) and high performance liquid chromatography-hydride generation-atomic fluorescence spectrometry (HPLC-HG-AFS), respectively. RESULTS: Arsenic accumulated in rat tissues especially in heart, liver, spleen, lung, kidney, uterus and ovary. Dimethylarsenic acid (DMA) was detected as the predominant species in rat plasma after dosing. In comparison of realgar, NHJDT with co-existing components significantly alleviated tissues injury, and reduced arsenic concentration in rat tissues and plasma. CONCLUSIONS: NHJDT with co-existing components combination was relatively safer than realgar, but the accumulation of arsenic was still significant after long-term medication. Therefore, great attentions should be paid to realgar-containing TCMs to avoid toxicity from arsenic accumulation. Moreover, the dose regimen of realgar-containing TCMs should be designed rationally for clinical application. These results may provide useful references for the application of realgar-containing TCMs and might be helpful for the understanding of TCM compound compatibility.

The Usefulness of Definitive Screening Design for a Quality by Design Approach as Demonstrated by a Pharmaceutical Study of Orally Disintegrating Tablet.

Definitive screening design (DSD) is a new class of small three-level experimental design that is attracting much attention as a technical tool of a quality by design (QbD) approach. The purpose of this study is to examine the usefulness of DSD for QbD through a pharmaceutical study on the preparation of ethenzamide-containing orally disintegrating tablet. Model tablets were prepared by directly compressing the mixture of the active pharmaceutical ingredient (API) and excipients. The five evaluated factors assigned to DSD were: the contents of API (X1) and lubricant (X2), and the compression force (X3) of the tableting process, the mixing time (X4), and the filling ratio of powder in the V-type mixer (X5). After tablet preparation, hardness and disintegration time were measured. The same experiments were performed by using the conventional design of experiments [i.e., L8 and L16 orthogonal array designs and central composite design (CCD)]. Results showed that DSD successfully clarified how various factors contribute to tablet properties. Moreover, the analysis result from DSD agreed well with those from the L8 and L16 experiments. In additional experiments, response surfaces for tablet properties were created by DSD. Compared with the response surfaces created by CCD, DSD could produce reliable response surfaces for its smaller number of experiments. We conclude that DSD is a powerful tool for implementing pharmaceutical studies including the QbD approach.

Simultaneous Evaluation of Dissolution and Permeation of Oral Drug Solid Formulations for Predicting Absorption Rate-Limiting Factors and In Vitro-In Vivo Correlations: Case Study Using a Poorly Soluble Weakly Basic Drug.

Combined dissolution and permeation systems are designed to simultaneously assess the dissolution of a pharmaceutical dosage form and the permeation of dissolved drugs therefrom. However, there were still some limitations on predicting the possible absorption rate-limiting steps and improving the in vitro-in vivo correlation (IVIVC) of a complete dosage form. In this study, the modified biorelevant media with some solubilizers and pH modifiers were integrated into the drug dissolution/absorption simulating system (DDASS). Indapamide, a poorly soluble compound (pKa = 8.8), was selected to validate the applicability of the modified biorelevant media. The elution and permeation dynamics of indapamide were investigated by using appropriate solubilizing agents in the DDASS. The absorption behaviors were analyzed after oral administration of indapamide in beagle dogs. The absorption rate-limiting steps and IVIVCs were predicted from the dissolution-permeation-absorption dynamic parameters. As a result, the absorption fraction of indapamide in the FaSSIFmod of DDASS was estimated to be approximately 100%, in accordance with its high permeability. The ratios of permeation rate to elution rate were 2.55 and 3.34 for the immediate- and sustained-release tablets of indapamide, respectively, suggesting a dissolution rate-limiting absorption for indapamine. In addition, point-to-point correlations were established between in vitro elution and in vivo absorption by the nonlinear and linear regression analysis ways (r > 0.85). The findings indicate that DDASS is a promising technique to develop improved IVIVCs of a complete dosage form, and the FaSSIFmod is suitable to predict the possible absorption rate-limiting steps of poorly soluble drugs in DDASS.

Effects of Lactobacillus reuteri-containing lozenges on healing after surgical removal of mandibular third molars: a randomised controlled trial.

We investigated the effect of probiotic supplements on oral wound healing, swelling, pain and discomfort after surgical removal of mandibular third molars. A second aim was to evaluate if the intervention could influence the concentrations of oxytocin in saliva. Sixty-four consecutive volunteers (18-34 years) were enrolled to a double-blind randomised placebo-controlled trial with two parallel arms. Following surgery, the patients were asked to take three lozenges per day containing two strains of Lactobacillus reuteri (DSM 17938 and ATCC PTA 5289) or placebo for two weeks. The clinical healing and extra-oral swelling were scored two weeks post-operatively. Samples of wound exudate were cultivated for the presence of Staphylococcus aureus and ß-haemolytic streptococci. Salivary oxytocin concentrations were analysed from pre- and post-surgery samples using ELISA technique. Compliance and the subjective perception of swelling, pain and discomfort were reported daily through visual analogue scales in a logbook. All patients except three completed the protocol and the postoperative course was uneventful in most cases. Minor extra-oral swellings were noted in five patients, but none required antibiotic treatment. At the 2-week follow-up, there were no significant differences in clinical wound healing index, extra-oral swelling, bacterial growth or salivary oxytocin levels between the groups. The self-reported data unveiled, however, a significantly reduced sense of swelling, in particular during the second week after surgery in the probiotic test group (P<0.05). Likewise, significantly fewer nights with disturbed sleep and fewer days with sick-leave from work were reported among the participants in the test group (P<0.05). No differences were found in the post-operative use of analgesics. In conclusion, we found no significant influence of probiotic supplements on objective wound healing after surgical extraction of impacted mandibular third molars. However, since the patients' perceived significant post-operative ameliorations, further studies are needed to explore the patient's value of the intervention.

Poly-pharmacokinetic strategy-delineated metabolic fate of bioactive compounds in a traditional Chinese medicine formula, Yuanhu Zhitong tablets, using parallel reaction monitoring mode.

OBJECTIVE: To evaluate the pharmacokinetics of eight constituents in Yuanhu Zhitong tablets, which may provide a method for the poly-pharmacokinetic study of traditional Chinese medicine. METHODS: A robust platform using Thermo Scientific™ Dionex™ UltiMate™ 3000 rapid separation LC, integrated with Thermo Scientific™ Q Exactive™ MS, was developed and validated to acquire, in a high-resolution full-scan mode, a global profile of all ionized components in rat plasma after oral administration of a suspension of Yuanhu Zhitong tablets. RESULTS: This robust UPLC-HRMS method was successfully applied for pharmacokinetic evaluation after oral administration of Yuanhu Zhitong tablets. The MS response showed a good linear relationship, with a coefficient of determination (r2) of >0.99. The levels of detection were in the range of 0.088-0.414 ng·ml-g for the different constituents. The recoveries ranged from 92.23% to 104.47%, and the matrix effect ranged from 85.24% to 101.02%. The intra- and inter-day accuracy was in the range of 0.00-12.54%, while the intra- and inter-day precision ranged from 0.44% to 7.63%. Short-term stability, long-term stability, freeze-thaw stability, and post-preparative stability ranged from -recision rangedThe time to reach peak plasma concentration (tmax) values for the analytes was less than 10 h, except that for tetrahydropalmatine, which was quickly absorbed into the bloodstream. The large area under the concentration-time curve (AUC) values (≥105 ng·h·l-g) for the eight compounds indicated good absorption and utility in rat plasma. The mean residence time was more than 6 h, indicating slow elimination. CONCLUSION: UPLC-HRMS was shown to be a very promising and powerful tool for the kinetic screening and characterization of compounds in medicinal herbs and traditional Chinese medicine formulas. Pharmacokinetic profiling of multiple compounds enables the clarification of metabolic processes and fates of the selected medicinal herbs or traditional Chinese medicine formula. This allows us to better understand the actions and associated therapeutic mechanisms of the traditional Chinese medicine.

Liquid Chromatography Method for the Simultaneous Quantification of Biotin and Vitamin B12 in Vitamin B Supplements.

Background: The determination of cyanocobalamin (vitamin B12) and biotin has always been challenging because of the lack of a chromophore for biotin and trace level input for vitamin B12 in supplements. Microbiological assay methods are currently used for quantitation. However, these methods are time consuming, may lack specificity, and have high imprecision. Objective: Our laboratory developed and validated an LC method for the simultaneous quantitation of vitamin B12 and biotin. Methods: This LC method uses a single quadruple mass analyzer to detect biotin and vitamin B12 at m/z 245.10 and m/z 678.29, respectively. Results: The mass analyzer allows for low limits of quantitation (biotin: 1 ng/mL; vitamin B12: 4 ng/mL). Precision results showed that injections are repeatable without the use of an internal standard (RSD < 5%). Single analyst (n = 5: RSD < 3%), within lab (n = 10: RSD < 8%), and multilab (n = 20: RSD < 13%) precision results were also much better than those reported by microbiological assay methods. Linearity was evaluated between 92.00 ng/mL and 9200 ng/mL (R² 09916) for biotin and between 4.846 ng/mL and 484.6 ng/mL (R² 0.9999) for vitamin B12. The method is accurate between 20 ng/mL and 60 ng/mL for vitamin B12 and between 400 ng/mL and 1200 ng/mL for biotin. Conclusions: The results show a simple, accurate, and precise method for the quantitation of vitamin B12 and biotin. Highlights: This work demonstrates that single quadrupole mass analyzers can be successfully used to quantify trace level analytes in quality control laboratories.

Protective effects of Liuweiwuling tablets on carbon tetrachloride-induced hepatic fibrosis in rats.

BACKGROUND: Liuweiwuling tablets (LWWL) are an herbal product that exerts remarkable effects on liver protection and aminotransferase levels, and they have been approved by the Chinese State Food and Drug Administration (CFDA). Clinical studies have found that LWWL can inhibit collagen production and reduce the levels of liver fibrosis markers in the serum. Thus, LWWL is expected to have beneficial effects in the treatment of liver fibrosis. The purpose of this study was to evaluate the pharmacological effects of LWWL. METHODS: Hepatic fibrosis was induced in rats via carbon tetrachloride (CCl4) treatment. The rats were treated twice weekly for 8 weeks with either 2 mL·kg- 1 body weight of a 50% solution of CCl4 in olive oil or olive oil alone by oral gavage. A subset of rats received daily intraperitoneal injections of either colchicine (0.2 mg/kg per day), LWWL (0.4, 1.6, or 6.4 g/kg per day), or vehicle (N = 12 for all groups) during weeks 9-12. The rats were sacrificed after 12 weeks. Pathological changes in hepatic tissue were examined using hematoxylin and eosin (H&E) and Sirius Red staining. Immunohistochemistry was performed to observe α-smooth muscle actin (α-SMA) and collagen type I (collagen I) protein expression. Western blotting was also used to detect α-SMA protein expression. Real-time quantitative reverse-transcription polymerase chain reaction (RT-qPCR) was used to detect transforming growth factor-1 (TGF-ß1), platelet-derived growth factor (PDGF), tissue inhibitor of metalloproteinase-1 (TIMP1), and tissue inhibitor of metalloproteinase-2 (TIMP2) mRNA expression. RESULTS: LWWL significantly reversed histological fibrosis and liver injury, reduced the hydroxyproline content in liver tissue, and decreased α-SMA and collagen I expression. LWWL also suppressed hepatic stellate cell (HSC) activation by reducing the expression of the profibrogenic factors TGF-ß1 and PDGF. The expression levels of TIMP1 and TIMP2, which regulate extracellular matrix (ECM) degradation, were decreased after CCl4 injury in LWWL-treated rats. CONCLUSIONS: These data suggest that LWWL may serve as a promising therapeutic agent to reduce fibrogenesis.

Health risk assessment of arsenic in Realgar and NiuHuangJieDu Tablets based on pharmacokinetic study.

NiuHuangJieDu Tablets (NHJDT), a popular realgar (As4S4) containing patented traditional Chinese medicine (TCM), is widely used in the treatment of acute tonsillitis, pharyngitis, periodontitis and mouth ulcer. However, arsenic is considered as one of the most toxic elements, leading to growing concerns about the quality and safety of realgar-containing TCMs recently. In this study, health risk assessment of arsenic in realgar and NHJDT was conducted through oral administration of both substances to rats with single and multiple doses, respectively. The total blood arsenic concentration was used as the health risk indicator and determined by hydride generation-atomic fluorescence spectrometry after modified Kjeldahl digestion, and then applied to the pharmacokinetic study. For single oral dose study in rats, the low, medium, and high doses of realgar and NHJDT were set equivalent to 1, 5 and 20 times the human therapeutic dose (1.3 mg realgar/kg), respectively. Multiple doses were given at low and high dose levels every 12 h for seven consecutive days, respectively. Significant differences in the total blood arsenic pharmacokinetic profiles were observed between the corresponding realgar and NHJDT groups. These results indicated that NHJDT significantly reduced the total blood arsenic exposure present in realgar, and the detoxification mechanism might be attributed to herb-herb interactions in NHJDT. However, the accumulation of blood total arsenic was significant due to the long elimination half-life and high accumulation index in both realgar and NHJDT groups. Therefore, the potential health risk of arsenic caused by the administration of realgar-containing TCMs should be taken into account for excessive or long-term medication. Precautions should be taken for the clinical application of realgar-containing TCMs.

Identify super quality markers from prototype-based pharmacokinetic markers of Tangzhiqing tablet (TZQ) based on in vitro dissolution/ permeation and in vivo absorption correlations.

BACKGROUND: A quality marker (Q-marker) is defined as an inherent chemical compound that is used for the quality control of a drug. Its biological activities are closely related to safety and therapeutic effects. Generally, a multiple-component herbal medicine may have many Q-markers. We therefore proposed a concept of "super Q-marker" satisfying both the criterion of Q-markers and PK-markers to be used in more effective quality control of herbal medicine. PURPOSE: The first aim was to find suitable prototype-based PK-markers from Tangzhiqing tablets (TZQ), a Chinese patent medicine. Then super Q-markers were expected to be identified from the prototype-based PK-markers based on an in vitro-in vivo correlation study. METHODS: Potentially eligible prototype-based PK-markers were identified in a single- and multiple-dose pharmacokinetic study on TZQ in 30 healthy volunteers. The in vitro dissolution and permeation profiles of the prototype-based PK-markers of TZQ were evaluated by the physiologically-based drug dissolution/absorption simulating system (DDASS). An in vitro-in vivo correlation analysis was conducted between the dissolution/permeation behaviors in DDASS and the actual absorption profiles in human to test the transferability and traceability of the promising super Q-markers for TZQ. RESULTS: In human, plasma paeoniflorin and nuciferine as prototype-based PK-markers exhibited the appropriate pharmacokinetic properties, including dose-dependent systemic exposure (AUC, Cmax) and a proper elimination half-life (1∼3h). In DDASS, it was predicted that paeoniflorin and nuciferine are highly permeable but the absorption rates are primarily limited by the dissolution rates. Moreover, the established in vitro-in vivo correlations of paeoniflorin and nuciferine were in support of the super Q-markers features. CONCLUSION: Paeoniflorin and nuciferine are identified as the super Q-markers from the prototype-based PK-markers of TZQ based on findings from a combination of in vitro, in vivo, and in vitro-in vivo correlation studies. This method is practical for optimal identification of qualified Q-markers, thus helping improve the quality control of herbal medicines.

Protective and restorative effects of the traditional Chinese medicine Jitai tablet against methamphetamine-induced dopaminergic neurotoxicity.

BACKGROUND: Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function. METHODS: Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization. RESULTS: Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels. CONCLUSIONS: Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Comparative pharmacokinetics study of five alkaloids in rat plasma and related compound-herb interactions mechanism after oral administration of Shuanghua Baihe tablets.

Shuanghua Baihe tablet is a traditional Chinese patent medicine which showed special advantages in the treatment of recurrent aphthous stomatitis. Scientists have improved and implemented the LC-MS/MS method, which is specific and sensitive, for comparative pharmacokinetics study of five alkaloids, including palmatine, berberine, epiberberine, jatrorrhizine and coptisine in rat plasma after oral administration of Rhizoma Coptidis extract and Shuanghua Baihe tablets. The results showed that Shuanghua Baihe tablets could promote the absorption of these five alkaloids and improved their bioavailability compared with R. Coptidis extract. To further investigate the related mechanism, everted intestinal sac model in vitro was used to indicate that alteration of in vivo pharmacokinetics of five alkaloids could be attributed to, at least in part, the absorption changes by coadministration of other herbs. These discoveries served as a theoretical basis for clinical use of Shuanghua Baihe tables.

Influence of polyvinylpyrrolidone, microcrystalline cellulose and colloidal silicon dioxide on technological characteristics of a high-dose Petiveria alliacea tablet.

PURPOSE: Petiveria alliacea L. (Phytolaccaceae) is a perennial shrub used by its immunomodulatory, anticancerogenic and anti-inflammatory properties. This study determined the influence of polyvinylpyrrolidone (PVP), colloidal silicon dioxide (CSD) and microcrystalline cellulose (MC) on the technological characteristic of a high-dose P. alliacea tablet prepared by the wet granulation method. METHODOLOGY: The botanical and pharmacognostic analysis of the plant material was firstly performed, followed by a 23 factorial design considering three factors at two levels: (a) the binder (PVP) incorporated in formulation at 10% and 15% (w/w); (b) the compacting agent (CSD) added at 10% and 15% (w/w) and; (c) the diluent (MC) included at 7.33% and 12.46% (w/w). The analysis of pharmaceutical performance and the accelerated and long-term stability of the best prototype were also completed. RESULT AND DISCUSSION: The binder, compacting agent and the interaction binder/diluent had a significant impact on breaking force of high-dose P. alliacea tablet. The optimum formula was found to contain 15% (w/w) of CSD, 7.33% (w/w) of MC and 10% (w/w) of PVP. At these conditions, the tablet shows a breaking force of 77.96 N, a friability of 0.39%, a total phenol content of 1.30 mg/tablet and a maximum disintegration time of 6 min. CONCLUSIONS: The use of adequate amounts of PVP, MC and CSD as per the factorial design allowed the preparation of a tablet suitable for administration, despite the inappropriate flow and compressibility properties of the P. alliacea powder.

Characterisation of zinc delivery from a nipple shield delivery system using a breastfeeding simulation apparatus.

Zinc delivery from a nipple shield delivery system (NSDS), a novel platform for administering medicines to infants during breastfeeding, was characterised using a breastfeeding simulation apparatus. In this study, human milk at flow rates and pressures physiologically representative of breastfeeding passed through the NSDS loaded with zinc-containing rapidly disintegrating tablets, resulting in release of zinc into the milk. Inductively coupled plasma optical emission spectrometry was used to detect the zinc released, using a method that does not require prior digestion of the samples and that could be applied in other zinc analysis studies in breast milk. Four different types of zinc-containing tablets with equal zinc load but varying excipient compositions were tested in the NSDS in vitro. Zinc release measured over 20 minutes ranged from 32-51% of the loaded dose. Total zinc release for sets tablets of the same composition but differing hardness were not significantly different from one another with P = 0.3598 and P = 0.1270 for two tested pairs using unpaired t tests with Welch's correction. By the same test total zinc release from two sets of tablets having similar hardness but differing composition were also not significantly significant with P = 0.2634. Future zinc tablet composition and formulation optimisation could lead to zinc supplements and therapeutics with faster drug release, which could be administered with the NSDS during breastfeeding. The use of the NSDS to deliver zinc could then lead to treatment and prevention of some of the leading causes of child mortality, including diarrheal disease and pneumonia.

Investigating the potential of Tamarindus indica pectin-chitosan conjugate for reducing recovery period in TNBS induced colitis.

The present study was aimed at exploiting the wound healing applications and tablet coating potential of Tamarindus indica pectin-chitosan (PCH) conjugate for reducing recovery period from TNBS induced colitis. The PCH (60:40, 3% w/v) solution when spray coated followed by drying at 50°C created hydrophobic surface, that may be due to interaction of pectin with chitosan as evident from temperature ramping rheological investigations. Further, the 15% w/v coating was sufficient to prevent Mesalamine (Ma) release in pH 1.2. The AUC and AUMC of PCH coated tablets were 1.98 and 17.69 fold increased as compared to uncoated tablets. A synergistic therapeutic effect of PCH conjugate with Ma was evident from the colon/body weight ratio, clinical activity and damage score. Overall, the findings suggested PCH and Ma (20mg) reduces the recovery period from 5 to 4days with reduction in dose.

Preparation of Orally Disintegrating Tablets Containing Powdered Tea Leaves with Enriched Levels of Bioactive Compounds by Means of Microwave Irradiation Technique.

In the present study, a microwave treatment process has been applied to prepare orally disintegrating tablets (ODTs) containing powdered tea leaves with enriched levels of the anti-inflammatory compounds such as chafuroside A (CFA) and chafuroside B (CFB). The use of distilled water as the adsorbed and granulation solvents in this preparation process afforded tablets with a long disintegration time (more than 120 s). The CFA and CFB contents of these tablets did not also change after 4 min of microwave irradiation due to the tablet temperature, which only increased to 100°C. In contrast, the tablet temperature increased up to 140°C after 3 min of microwave irradiation when a 1.68 M Na2HPO4 solution instead of distilled water. Notably, the disintegration time of these tablets was considerably improved (less than 20 s) compared with the microwave-untreated tablets, and there were 7- and 11-fold increases in their CFA and CFB contents. In addition, the operational conditions for the preparation of the tablets were optimized by face-centered composite design based on the following criteria: tablet hardness greater than 13 N, disintegration time less than 30 s and friability less than 0.5%. The requirements translated into X1 (the amount of granulation solvent), X2 (tableting pressure) and X3 (content of the powdered tea leaves) values of 45%, 0.43 kN and 32%, respectively, and the ODTs containing powdered tea leaves prepared under these optimized conditions were found to show excellent tablet properties and contain enriched levels of CFA and CFB.

Tongluo Xingnao Effervescent Tablet preserves mitochondrial energy metabolism and attenuates cognition deficits in APPswe/PS1De9 mice.

Tongluo Xingnao Effervescent Tablet (TXET), a traditional Chinese herbal formula composed of Ligusticum chuanxiong hor, Scutellaria baicalensis Georgi and Angelica sinensis, has been widely used to treat Alzheimer's disease (AD) and related dementias for decades in China. In the present study, we investigated the effects of TXET on mitochondrial function, energy metabolism and cognitive amelioration in the APPswe/PS1De9 transgenetic mouse model of AD. The energy charge and phosphocreatine, activity of the mitochondrial electron transport chain complexes, mitochondrial membrane potential, activity of Na(+)-K(+) ATPase and the expression levels of Bcl-2 and Bax in the brains were measured, respectively. TXET exhibits significant protection on mitochondrial function and energy supply in addition to ameliorating cognitive decline in APPswe/PS1De9 mice. TXET rescues mitochondrial function by increasing the mitochondrial membrane potential, energy charge levels, activity of respiratory chain complexes and Na(+)-K(+) ATPase activity. These findings suggest that TXET may attenuate cognition impairment through the restoration of mitochondrial function and energy metabolism in the brains in APPswe/PS1De9 mice.

Predicting biopharmaceutical performance of oral drug candidates - Extending the volume to dissolve applied dose concept.

The purpose of the study was to experimentally deduce pH-dependent critical volumes to dissolve applied dose (VDAD) that determine whether a drug candidate can be developed as immediate release (IR) tablet containing crystalline API, or if solubilization technology is needed to allow for sufficient oral bioavailability. pH-dependent VDADs of 22 and 83 compounds were plotted vs. the relative oral bioavailability (AUC solid vs. AUC solution formulation, Frel) in humans and rats, respectively. Furthermore, in order to investigate to what extent Frel rat may predict issues with solubility limited absorption in human, Frel rat was plotted vs. Frel human. Additionally, the impact of bile salts and lecithin on in vitro dissolution of poorly soluble compounds was tested and data compared to Frel rat and human. Respective in vitro - in vivo and in vivo - in vivo correlations were generated and used to build developability criteria. As a result, based on pH-dependent VDAD, Frel rat and in vitro dissolution in simulated intestinal fluid the IR formulation strategy within Pharmaceutical Research and Development organizations can be already set at late stage of drug discovery.