Impact of Bladder Wall Thickness on the Outcomes of Antimuscarinic Treatment in Women with Overactive Bladder

<b><i>Aim:</i></b> This study aimed to evaluate the effect of bladder wall thickness (BWT) (using transabdominal ultrasound) on the outcomes of antimuscarinic treatment in women with overactive bladder. <b><i>Methods:</i></b> A total of 102 female patients with symptoms of OAB were recruited. All patients completed the Overactive Bladder version 8 (OAB-V8) (Arabic validation) and the International Consultation of Incontinence Questionnaire (ICIQ-SF). Patients completed the urodynamic study (UDS) including uroflowmetry and PVR and measures of BWT by transabdominal ultrasound. The patients were classified into 2 major groups: G1 (patients with BWT &#x3c;5 mm) and G2 (patients with BWT ≥5 mm). The patients were re-evaluated after 3-month medication with solifenacin 10-mg oral tablet. <b><i>Results:</i></b> At baseline, the results of OAB-V8 and ICIQ-SF were significantly higher in G2 than G1 (<i>p</i> &#x3c; 0.001). Regarding UDS, volume at 1st desire to void, volume at strong desire to void, and MBC were significantly higher in group 1 compared to group 2 (<i>p</i> = 0.001). Intravesical pressure at strong desire and patients’ number of DO were significantly increased in G2 (<i>p</i> &#x3c; 0.05 and <i>p</i> = 0.001, respectively). After treatment, there was an improvement in both groups regarding OAB-V8, ICIQ-SF, bladder volume at 1st desire to void, bladder volume at strong desire to void, bladder volume at DO, MBC, intravesical pressure at strong desire, and the patients’ number with DO (decreased), and these improvements were statistically significant in group 1 compared to group 2 (<i>p</i> &#x3c; 0.05). <b><i>Conclusion:</i></b> BWT showed a significant association with both OAB symptom scores and UDS parameters. The decrease in BWT is associated with a significantly higher response to solifenacin therapy regarding the UDS results.

OPTIMIZED FAST DISINTEGRATING TABLETS, BOOSTED OSELTAMIVIR PHOSPHATE ORALLY FAST DISINTEGRATING TABLETS

Background Around 33% of the populace (fundamentally pediatric and geriatric) has gulping hardships, bringing about helpless consistence with oral tablet drug treatment which prompts decreased in general treatment viability. For this explanation, tablets that can quickly break down or deteriorate in the oral cavity have drawn in a lot of consideration. Objective research was designed to develop and evaluate boosted orally fast disintegrating tablets (OFDT) for oro-buccal drug delivery of oseltamivir phosphate. Methods In the present study six formulations of mouth dissolving tablet of oseltamivir were prepared by direct compression method using SSG as a super disintegrating agent with lactose, talcum, mannitol, SLS and starch. The prepared tablets were then subjected to various evaluation parameters. Results every one of the outcomes was observed to be inside satisfactory reaches. The formulation F6 manufacturing utilizing SSG 50mg and SLS 10mg showed the higher medication content (98%), while the formulation F2 showed the least medication content (92%). It was seen that with the increment in SSG concentration, the medication content was additionally increased. SEM concentrate on showed request of expanding unpleasantness of tablet surface is F1<F2<F3<F4<F5<F6. The expanding unpleasantness may be answerable for higher % of medication release. Formulation F1 showed the most elevated medication discharge (97.735%), while the formulation F5 showed the least medication discharge (56.24%). Finally, it was inferred that SSG, SLS, D-mannitol, starch, lactose, and talcum powder can be effectively utilized in the formulation of Oseltamivir phosphate mouth dissolving tablets. Conclusion: From the above work it was presumed that the formulation of the Oseltamivir Phosphate was observed to be more achievable than the regular one.

First Year Comparison of Sickle Cell Pediatric Cohorts from Haiti and Miami (CSHSCD Multicenter Study): Baseline Data

Background: The NIH-sponsored observational study "Comparative Study of Haiti and Miami Cohorts of Sickle Cell Disease CSHSCD" (R01HL149121) coordinates the follow up of children with sickle cell disease (SCD) in Haiti and compares it to a Miami cohort of children of either Haitian or African American ethnicity for the purpose of assessing barriers through questionnaires and examining differences in the care received in their respective environments. Methods: Children less than 6 years of age with SCD are eligible for enrollment in five participating sites: University of Miami (UM, Miami, Florida), Hôpital Saint Damien (HSD, Tabarre, Haiti), Hôpital de l' Université d'Etat d'Haïti (HUEH, Port-au-Prince, Haiti), Hôpital Universitaire Justinien (HUJ, Cap Haitien, Haiti), and Hôpital Sacré Coeur (HSC, Milot, Haiti). Medians and interquartile ranges or percentages were compared at baseline regarding demographics, clinical and growth parameters, laboratory tests, and the children's hydroxyurea (HU) utilization during the first year of enrollment (May 25, 2020-May 24,2021). A Likert-scale barrier questionnaire was distributed at baseline to assess differences in healthcare access. A P value &lt;0.05 was considered statistically significant to establish differences. Results: 130 children were enrolled during the reported period. Significant differences were observed in age, weight percentiles, hemoglobin levels, pain rates, HU treatment, and pneumococcal vaccination. Penicillin prophylaxis was always given by oral route in Miami, but only 39.8% times in Haiti, with 58% of children receiving prophylaxis by intramuscular injection every month and 2.2% (N=2 children) with either unknown or not receiving prophylaxis. Previous medication outsourcing accounted for the oral tablet form in Haiti. Parents in Haiti had more barriers regarding not able to afford treatment (21.5% compared to 8.1% in Miami) and had similar responses regarding not able to afford coming to clinic (21.5% vs. 18.9%). Parents in Miami expressed living far away from clinic (70.2% compared to 25.8% in Haiti), but had more help from other family members (78.4% vs. 33.3%). Interestingly, parents in Miami did not know sometimes what to do when the child was sick (40% respondents vs. 11% in Haiti). There were no major differences between the responses from the African Americans and Haitians living in Miami, except for not knowing sometimes what to do when child is sick (African-Americans having less doubts than Haitians; 25% vs. 52.6%). In short-term follow up, no enrolled children died, although two eligible children in Haiti died before enrollment. One child developed COVID-19 in Miami with only mild symptoms, which resolved. Conclusion: At entry children in Haiti are older, weigh less, are more anemic, have more pain episodes, and fewer receive hydroxyurea treatment. Under-vaccination with pneumococcal 13-valent conjugate (Prevnar-13) is notable in Haiti. There were significant differences detected on the barrier questionnaire among respondents in both countries. Acknowledgment: We acknowledge NHLBI for supporting this work. Figure 1 Figure 1. Disclosures Alvarez: GBT: Membership on an entity's Board of Directors or advisory committees; Forma Therapeutics: Membership on an entity's Board of Directors or advisory committees.

589. Oral Tablet Vaccination Induces Heightened Cross-Reactive CD8 T Cell Responses to SARS-COV-2 in Humans

Background Covid-19 has accelerated global demand for easily distributed vaccines. Furthermore, as variant SARS-CoV-2 strains that circumvent antibody responses emerge, cross-protective vaccines provide substantial public health benefits. Vaxart is developing a shelf stable oral tablet vaccine that incorporates both the spike (S) and the more conserved nucleocapsid (N) proteins. Vaxart’s vaccine platform uses a non-replicating adenovirus and a TLR3 agonist as an adjuvant. Methods In an open-label phase 1 clinical study, 35 healthy subjects received either a single low (1x1010 IU; n=15) or high (5x1010 IU; n=15) dose of the vaccine candidate VXA-CoV2-1 with a small cohort receiving 2 low doses. PBMCs were taken at pre- and 7 days post-vaccination and restimulated with S and N peptides from SARS-CoV-2 or the 4 human endemic coronaviruses (HCoV). Cells were stained for CD4/CD8/CD107a (surface) and IFNγ/TNFα (intracellular). Subjects that received an intramuscular (i.m.) mRNA vaccine had PBMCs taken at the same timepoints and were compared in the same assay. Results The study’s results indicate that the VXA-CoV2-1 tablet was well tolerated. The majority of subjects had an increase in S-specific anti-viral CD8+ T cell responses. 19/26 (73%) subjects had a measurable CD8+ T cell response on day 8 above baseline, on average 1.5-4.6%. In a comparator experiment with the 2 SARS-CoV-2 i.m. mRNA vaccines, VXA-CoV2-1 outperformed other vaccine candidates with a &gt;3.5-fold increase in S specific antiviral CD8 T cell responses. T cell responses specific to the 4 endemic HCoV were increased by 0.6% in subjects given VXA-CoV2-1. Conclusion Here we describe a room temperature stable tablet that induces SARS-CoV-2 S specific CD8 T cells of high magnitude after one dose in humans. Overall, the level of antiviral SARS-CoV-2 specific T cells, particularly IFNg-producing CD8s, induced following oral immunization with VXA-CoV2-1 are of higher magnitude than the mRNA vaccines currently in use against COVID-19. T cell responses against 4 endemic HCoV were also induced. Because T cells may be important in protecting against death and severe infection, these results suggest that VXA-CoV2-1 could be cross-protective against a wide array of emerging pandemic coronaviruses. Disclosures Susan Johnson, PhD, Vaxart (Employee) Clarissa Martinez, MPH, Vaxart (Employee) Mario Cortese, PhD, Vaxart (Employee) Josefina Martinez, n/a, Vaxart (Employee) Shaily Garg, BS, Vaxart (Employee) Nadine Peinovich, MPH, Vaxart (Employee) Emery Dora, n/a, Vaxart (Employee) Sean Tucker, PhD, Vaxart (Employee)

Pharmacokinetics and diuretic effect of furosemide after single intravenous, oral tablet, and newly developed oral disintegrating film administration in healthy beagle dogs

Background Furosemide, a diuretic that acts on the loop of Henle, is commonly used to treat congestive heart failure in veterinary medicine. Some owners have difficulty in administering oral tablet medication to animal patients, which leads to noncompliance, especially during long-term administration. Oral disintegrating film (ODF) has the advantages of easy administration via a non-invasive route, rapid dissolution, and low suffocating risk. The objective of this study was to research the pharmacokinetic (PK) profiles and diuretic effect of furosemide after intravenous (IV), orally uncoated tablet (OUT), and newly developed ODF administration in healthy beagle dogs. In this study, a furosemide-loaded ODF (FS-ODF) formulation was developed and five beagle dogs were administered a single dose (2 mg/kg) of furosemide via each route using a cross-over design. Results The most suitable film-forming agent was sodium alginate; thus, this was used to develop an ODF for easy drug administration. No significant differences were detected in the PK profiles between OUT and FS-ODF. In the blood profiles, the concentration of total protein was significantly increased compared to the baseline (0 h), whereas no significant difference was detected in the concentration of creatinine and hematocrit compared to the baseline. FS-ODF resulted in a similar hourly urinary output to OUT during the initial 2 h after administration. The urine specific gravity was significantly decreased compared to the baseline in each group. The peak times of urine electrolyte (sodium and chloride) excretion per hour were 1 h (IV), 2 h (OUT), and 2 h (FS-ODF). Conclusions These results suggest that the PK/PD of furosemide after administration of newly developed FS-ODF are similar to those of OUT in healthy dogs. Therefore, the ODF formulation has the benefits of ease and convenience, which would be helpful to owners of companion animals, such as small dogs (< 10 kg), for the management of congestive heart failure.

OPTIMASI FORMULA TABLET BUKAL MUKOADHESIVE GLIBENKLAMID MENGGUNAKAN MATRIKS CMC NA SERTA ASAM OLEAT SEBAGAI ENHANCHER

Glibenclamide is a sulfonylurea class of antidiabetic drugs that works by stimulating insulin secretion in the pancreas so that it is effective only when the β-cells of the pancreas can still produce. The glibenclamide dosage form that is on the market is a conventional oral tablet which has various disadvantages in terms of pharmacokinetics. Based on this, it is necessary to develop a more effective drug delivery system for glibenclamide in order to avoid first-pass metabolism so as to increase the bioavailability of glibenclamide, namely by making mucoadhesive buccal tablets. This glibenclamide mucoadhesive buccal tablet is formulated using a variety of mucoadhesive polymers, namely CMC Na and oleic acid as enhancers. The manufacture of four mucoadhesive buccal tablet formulas used the direct compression method. The results of the weight uniformity test showed that they did not meet the NP requirements specified, all formulas had an NP of more than 15. The tablet hardness test also showed results that did not meet the test requirements. However, the results of the physical properties of the brittleness, pH and swelling index showed the results that met the test requirements. In this research, the optimum variation of CMC Na polymer and oleic acid as enhancers to physical properties (hardness, brittleness, pH, swelling ability) and the release of glibenclamide mucoadhesive tablets were CMC Na of 37.5 mg and oleic acid of 3.5. ml.

Viable and Heat-Killed Probiotic Strains Improve Oral Immunity by Elevating the IgA Concentration in the Oral Mucosa

Oral-nasal mucosal immunity plays a crucial role in protecting the body against bacterial and viral invasion. Safe probiotic products have been used to enhance human immunity and oral health. In this study, we verified the beneficial effects of mixed viable probiotic tablets, consisting of Lactobacillus salivarius subsp. salicinius AP-32, Bifidobacterium animalis subsp. lactis CP-9, and Lactobacillus paracasei ET-66, and heat-killed probiotic tablets, consisting of L. salivarius subsp. salicinius AP-32 and L. paracasei ET-66, on oral immunity among 45 healthy participants. Participants were randomly divided into viable probiotic, heat-killed probiotic, and placebo groups. The administration of treatment lasted for 4 weeks. Saliva samples were collected at Weeks 0, 2, 4, and 6, and Lactobacillus, Bifidobacterium and Streptococcus mutans populations and IgA concentration were measured. IgA concentrations, levels of TGF-beta and IL-10 in PBMCs cells were quantified by ELISA method. Results showed that salivary IgA levels were significantly increased on administration of both the viable (119.30 ± 12.63%, ***P < 0.001) and heat-killed (116.78 ± 12.28%, ***P < 0.001) probiotics for 4 weeks. Among three probiotic strains, AP-32 would effectively increase the levels of TGF-beta and IL-10 in PBMCs. The oral pathogen Streptococcus mutans was significantly reduced on viable probiotic tablet administration (49.60 ± 31.01%, ***P < 0.001). The in vitro antibacterial test confirmed that viable probiotics effectively limited the survival rate of oral pathogens. Thus, this clinical pilot study demonstrated that oral probiotic tablets both in viable form or heat-killed form could exert beneficial effects on oral immunity via IL-10, TGB-beta mediated IgA secretion. The effective dosage of viable probiotic content in the oral tablet was 109 CFUs/g and the heat-killed oral tablet was 1 × 1010 cells/g.

The potential of banana fruit Ranggap (Musa paradisiaca var. Troglodytarum) as an excipient alternative to oral tablet dosage form

Introduction: Starch is one of the ingredients that has many benefits, including in the pharmaceutical field, especially as a pharmaceutical excipient in pharmaceutical formulations. Aim: This study aims to isolate, characterise, and formulate the starch of banana fruit (Musa paradisiaca var. Troglodytarum) into tablet dosage forms. Methods: The characteristics of the perceived banana starch can be said to be comparable to that of corn starch so that it is expected to be used as a source of starch which can be used as a pharmaceutical excipient. The starch of isolated banana fruit was used as a filler, binder, and crusher in the wet granulation method tablet formulations with concentrations of 2%, 3%, and 5%. Results: The physicochemical characteristics of starch isolated from banana fruit are considered to meet the requirements of pharmaceutical excipients required in the Handbook of Pharmaceutical Excipients 6th edition and the United States Pharmacopeia 32nd edition. Conclusion: Of the total formulas tested, tablets with binder content of banana starch 3%, 5% and 10% corn starch meet the tablet evaluation requirements.