Dosage Units Research Articles

Impact of metrological correlation on the total combined risk in pharmaceutical equivalence evaluations

Pharmaceutical equivalence evaluation requires a multiparametric conformity assessment for both generic and reference medicines. This paper investigates the impact of metrological correlations on the total combined risk in pharmaceutical equivalence evaluations. The study focused on the equivalence between ranitidine hydrochloride tablets, assessed by determining the average weight, the assay of the active pharmaceutical ingredient, and the uniformity of dosage units. The risks of false conformity decisions were evaluated using Monte Carlo method simulations across four scenarios, each reflecting different correlation conditions. The results of the study focus on evaluating pharmaceutical equivalence between ranitidine hydrochloride tablets from two manufacturers. The tablets were tested for three parameters: average weight, active pharmaceutical ingredient (API) assay, and uniformity of dosage units. The measured values were within the regulatory specifications for both medicines A and B. Four scenarios of metrological correlation were assessed: #1 – actual correlation from shared analytical steps, #2 – correlation between parameters within the same medicine, #3 – correlation between generic and reference medicines, and #4 – uncorrelated parameters. The study revealed that correlations significantly affect total and combined risk values. The correlations between different parameters of the same medicine affect the total risk values, while the correlations between generic and reference medicines for a given parameter influence the combined particular risk values. Correlations between parameters of the same medicine affect total risk values, while correlations between generic and reference medicines impact combined particular risk values. Both types of correlations significantly influence combined total risk values, making metrological correlations crucial in pharmaceutical equivalence evaluations. Proper consideration of these correlations ensures the quality, efficacy, and safety of generic and reference medicines.

B-335 Analytical Performance of the Novel EQA Material for Fecal Immunochemical Test for Hemoglobin

Abstract Background EQA (external quality assurance) program for FIT (fecal immunochemical test for hemoglobin) is performed in many countries, and its demand increases as FIT is widely used in organized colorectal cancer screening programs. The materials used in FIT EQA vary from buffer-based liquid control, and lyophilized stool, to material that mimics stool, artificial stool. We could not find ideal EQA material with hemoglobin uniformly contained, good stability of hemoglobin, and ease in use such as ready-to-use form. The merit to use material that simulates actual sample, stool, is not only to be compliant with ISO15189 but also to suit various methods and sampling devices in FIT. The development of artificial stool material has been awaited by laboratories using FIT to evaluate errors and precisions in specimen collection.We assessed the analytical performance of the new artificial stool developed in HECTEF (Health Care Technology Foundation) to evaluate this artificial stool material was suitable as an EQA material. We examined the following three points: 1) Sample collection, 2) Uniformity, and 3) Stability of hemoglobin. Methods 1) Sample collection: The material was collected with the sampling probes of OC-Auto Sampling Bottle 3 (Eiken Chemical) and the collection amount was calculated by comparing the weight before and after sampling the artificial stool. 2) Uniformity: The uniformity of hemoglobin was evaluated during production before and after bottling based on “Uniformity of dosage units” section of The Japanese Pharmacopoeia 18th edition, 2021. The material was sampled from 10 different points and hemoglobin concentrations were measured using OC-Sensor DIANA. The uniformity of hemoglobin between the vials was evaluated by calculating the CV from the average of hemoglobin concentrations from samples of three points from three vials. 3) Stability of hemoglobin: The materials stored under different temperature conditions were compared with the material stored frozen at -20 °C. Storage conditions were at refrigeration for 20 months, at 30 °C for 1 month, and freeze-thawing for five times. Evaporation from the material was evaluated by weighing the samples before and after storage at 30 °C for 1 month. Results 1) Sample collection: The material was collected with sampling probes and the collection amounts were 106% (compared to theoretical amount).2) Uniformity: Uniformity of hemoglobin during production was within the specification of “Uniformity of dosage units” section of the pharmacopoeias, acceptance value<15.0. Uniformity of hemoglobin among three vials was within ±10% CV.3) Stability of hemoglobin: Stabilities of the material were all within ±10% from the control material (frozen) after storage at all temperature conditions. Evaporation from the material in a vial was below 1% at 30 °C storage for 1 month. Conclusions This artificial stool is suitable for EQA material because it is confirmed that it shows favorable analytical results in sample collection, uniformity, and stability of hemoglobin. The evaluation of this material in the EQA program to show its suitability was performed by Labquality. The result is reported in a poster at ADLM 2024.

The impacts of roller compaction on the quality attributes of simultaneously compressed micro and minitablets

The challenges of developing good quality low dose minitablets was assessed by systematically studying the effects of ibuprofen (IBU, a model compound) particle sizes (6–58 µm D50) and concentrations (0.1–3 %w/w), roller compaction forces (3–7 kN/cm), and the minitablet sizes (1.2, 1.5 and 2 mm diameter). A novel compression approach, where all three minitablet sizes were simultaneously produced in a single compression run was used. Roller compacted ribbons, granules, minitablets were characterized for physico-mechanical properties and minitablets were also characterized for stratified content uniformity and weight uniformity. The results showed that roll force was the more dominant factor to ribbon solid fraction or tensile strength and granule size enlargement. Minitablets obtained from the granules had good weight uniformity; all but one batch met the <Ph. Eur. 2.9.5 > criteria. The precise control of tooling lengths across the various sizes was found profoundly important for achieving expected weights, solid fraction, and tensile strength of the simultaneously produced minitablets. The roller compaction process considerably improved the CU variability of the minitablets as compared to the direct compression process. Smaller particle size and higher concentration of IBU, increased roller compaction force, and larger minitablet size improved the potency and content uniformity; however, only the minitablet size was a statistically significant factor in this study. As a product strategic design criterion, a threshold of 25 minitablets in a dosage unit would ensure robust downstream filling and weight verification operations as well as dose accuracy and uniformity (would pass <USP 905> stage 1 criteria). This study results demonstrated feasibility of the novel simultaneous compression approach and the roller compaction process in developing good quality minitablets.

Post-marketing quality surveillance of selected antibacterial agents marketed in porous borders; the case of Ethiopia-Sudan-Eritrea border.

The presence of poor-quality medicines is becoming a public health threat in many parts of the world, particularly in developing countries. Antibiotics are among the most common anti-infective medicines that are highly prone to this problem. The purpose of this study was to assess the quality of selected antibacterials that are marketed in Setit Humera and West Gondar Zones, North West Ethiopia, which are located on the Ethiopian side of the Ethiopia-Sudan-Eritrea border. Seventy-one samples of the four antibacterial medicines (Ciprofloxacin, Norfloxacin, Amoxycillin, and Amoxycillin clavullanate combination) were collected from six sites in Setit Humera and West Gondar Zones, North West Ethiopia. A mystery shopping system was used for sample collection. Visual inspections and confirmation of the registration status were carried out using the joint WHO/FIP/USP checklist and the Ethiopian Food and Drug Authority's (EFDA's) Electronic Regulatory Information System (eRIS), respectively. Then Pharmacopeial methods (USP, BP) were employed to assess the physicochemical quality parameters. During the period of our data collection, the application status for registration in the eRIS system was checked. From 71 samples, 25.35% (18/71) were not registered, and 15.49% (11/71) were registered, but the license period had expired. Some samples (12.06% (17/71)) did not meet the visual inspection criteria. The physicochemical evaluation showed that all the samples studied met the quality specifications for the identification and hardness tests. However, concerning assay, dissolution, uniformity of dosage units, disintegration, and friability test parameters, 27.49% (23/71), 16.9% (12/71), and 14.08% (10/71), 2.82% (2/71) and 8.57% (3/35) of samples were found to be substandard, respectively. Overall, 56.33% (40/71) of the samples tested were of poor quality, failing to meet any one or more of the assessed parameters in this study. The study indicated that poor-quality antibacterial medicines are circulating in the study sites. Therefore, even if the area was affected by conflict at the time of the study, the regulatory bodies should focus on enforcing the necessary measures by collaborating with the regional and national regulatory medicine agencies to ensure that the antibacterial medicines available meet the required mandatory minimum standards.

Factorial design-aided derivatization-free fluorimetric ultrasensitive assay of vonoprazan with application in uniformity of dosage units and plasma samples analysis: Comprehensive and comparative greenness and whiteness assessment

This study presents a novel derivatization-free spectrofluorimetric method for the quantification of vonoprazan (VPZ) that is characterized by its high sensitivity, environmental friendliness, and cost-effectiveness. Notably, this method eliminates the requirement for pre-derivatization, extraction procedures, large amounts of organic solvents, and/or expensive instrumentation, which distinguishes it from previous approaches. The approach employed in this study relies on the formation of an association complex between VPZand the xanthene dye acid red 87 (AR87) under acidic conditions. The stability of the VPZ-AR87 complex was determined to be remarkably high, with a complex formation constant (Kf) value exceeding 2 x 106 M−1. The fluorimetric measurements rely on the quantitative and selective quenchingof the dye’s native fluorescence emission at 545 nm. The experimental parameters were optimized utilizing a quality-by-design 23 full factorial design. This strategy yielded a highly favorable linearity range of 10.0 to 400.0 ng/mL, with a correlation coefficient (r) of 0.9997. The presented methodology exhibited a high level of sensitivity, as evidenced by its ability to detect concentrations as low as 1.2 ng/mL. This sensitivity enabled its successful application for the estimation of VPZ in human plasma samples with high %recoveries (98.21–101.67) and low %RSD values (<1.52). Furthermore, content uniformity testing of low-dose VPZ tablets was performed according to United States Pharmacopeia guidelines. Greenness and whiteness metrics analysis showed a significant advantage of the proposed method over previously reported fluorimetric methods. Validation of the developed approach was carried out in accordance with ICHQ2 (R1) guidelines.

Quality of medicines for Cardio-Vascular Diseases (CVDs) in the Ethiopian border with Kenya: The case of enalapril maleate and furosemide tablet quality in Borena and Gedeo zones.

Hypertension (HTN), a cardiovascular disease (CV), is a major public health challenge. Therefore, the quality of drugs used to treat it has become a major concern. Enalapril and furosemide are among the drugs prescribed to manage hypertension. Hence, this study is aimed at evaluating the quality of different brands of enalapril and furosemide tablets available in the Gedeo and Borena zones, southern Ethiopia. Thirteen generic brands of enalapril maleate (5 mg) and furosemide (40 mg) tablets were evaluated for visual defects, in vitro dissolution test, weight variations, friability, hardness, and disintegration tests. The analysis of active pharmaceutical ingredient (API) content was performed by high performance liquid chromatography (HPLC). Out of 55 samples, 7 (12.73%) failed to comply with the criteria for visual inspection; otherwise, all samples passed the identification test. Except for one brand of each of enalapril maleate and furosemide, all passed the dissolution test. The assay value showed that all enalapril maleate samples were within the limits of United States Pharmacopoeia (USP), 2020. Additionally, except for two batches, all furosemide samples were within the USP and British Pharmacopoeia (BP), 2020 standards. Out of 55 samples, 8% (2/25) and 6.67% (2/30) of enalapril maleate and furosemide tablets failed the uniformity of dosage units test per the USP-2020, respectively. All samples passed the disintegration test, and selected furosemide samples passed the microbial limit tests. However, 36% (9/25) and 20% (6/30) of enalapril maleate and furosemide samples failed to pass hardness test. Generally, from the total samples, 50.91% (28/55) were substandard (did not meet the specifications failing any one or more parameters assessed). The studied drugs circulating in the market did not meet some of the needed quality specifications. This could have brought a risk of reduced efficacy due to the distribution of poor quality medicines in the area.

Metformin drugs under simulated gastric conditions can generate high nitrite-dependent levels of N-nitrosodimethylamine

N-nitrosodimethylamine (NDMA) and N-nitrosodiethylamine (NDEA), group 2A carcinogens, were detected in finished drug products, including metformin, ranitidine, sartans and other drugs which caused multiple recalls in the USA and Europe. Important studies also reported the formation of NDMA when ranitidine and nitrite were added to simulated gastric fluid. Our objective was to screen finished drug products from Europe and USA for nitrosamine impurities and investigate the formation of NDMA in metformin finished drug products when added to simulated gastric fluid. One dosage unit of 30 different commercially available drugs, including metformin, sartans, and ranitidine were tested for NDMA, NDEA, and dimethylformamide (DMF) impurities, using a liquid chromatography-mass spectrometry (LC–MS) method. Then, 6 metformin finished drug products were tested in stomach conditions for 2 h at 37 °C in a 100 mL solution with a pH of 2.5 and different nitrite concentrations (40, 10, 1, 0.1 mM) and tested for NDMA, and DMF using LC–MS. We measured NDMA, NDEA, and DMF in 30 finished drug products. NDMA and DMF were quantified for metformin drug products in simulated gastric fluid with different nitrite concentrations. None of the 30 drugs showed concerning levels of NDMA, NDEA, or DMF when tested as single tablets. However, when metformin tablets are added to simulated gastric fluid solutions with high nitrite concentrations (40 mM and 10 mM), NDMA can reach amounts of thousands of nanograms per tablet. At the closest concentration to physiologic conditions we used, 1 mM, NDMA is still present in the hundreds of nanograms in some metformin products. In this in vitro study, nitrite concentration had a very important effect on NDMA quantification in metformin tablets added to simulated gastric fluid. 1 mM nitrite caused an increase above the acceptable daily intake set by the U.S. Food and Drug Administration (FDA) for some of the metformin drugs. 10 mM, 40 mM nitrite solutions generated NDMA amounts exceeding by more than a hundred times the acceptable daily intake set by the FDA of 96 nanograms. These findings suggest that metformin can react with nitrite in gastric-like conditions and generate NDMA. Thus, patients taking metformin could be exposed to NDMA when high nitrite levels are present in their stomach, and we recommend including a statement within the Patient Package Inserts/Instructions for use.

Developing an innovative 3D printing platform for production of personalised medicines in a hospital for the OPERA clinical trial

Breast cancer is the most frequently diagnosed cancer in women worldwide, and non-adherence to adjuvant hormonotherapy can negatively impact cancer recurrence and relapse. Non-adherence is associated with side effects of hormonotherapy. Pharmacological strategies to mitigate the side effects include coadministration of antidepressants, however patients remain non-adherent. The aim of this work was to develop medicines containing both hormonotherapy, tamoxifen (20 mg), along with anti-depressants, either venlafaxine (37.5 or 75 mg) or duloxetine (30 or 60 mg), to assess the acceptability and efficacy of this personalised approach for mitigating tamoxifen side effects in a clinical trial. A major criterion for the developed medicines was the production rate, specified at minimum 200 dosage units per hour to produce more than 40,000 units required for the clinical trial. A novel capsule filling approach enabled by the pharmaceutical 3D printer M3DIMAKER 2 was developed for this purpose. Firstly, semi-solid extrusion 3D printing enabled the filling of tamoxifen pharma-ink prepared according to French compounding regulation, followed by filling of commercial venlafaxine or duloxetine pellets enabled by the development of an innovative pellet dispensing printhead. The medicines were successfully developed and produced in the clinical pharmacy department of the cancer hospital Gustave Roussy, located in Paris, France. The developed medicines satisfied quality and production rate requirements and were stable for storage up to one year to cover the duration of the trial. This work demonstrates the feasibility of developing and producing combined tamoxifen medicines in a hospital setting through a pharmaceutical 3D printer to enable a clinical trial with a high medicines production rate requirement.

Costs and access barriers to ondansetron: A national analysis of Medicare part D and Medicare Advantage plans.

e23126 Background: Seniors living with cancer and receiving prescription drug benefits through Medicare Part D Prescription Drug Plans (PDPs) can face cost and access barriers in the forms of prior authorization and quantity limit policies. While over half of Medicare beneficiaries are now insured with drug benefits through Medicare Advantage, it remains unclear how costs and access barriers compare between PDPs and MA drug plans (MADPs). This study compared plan-level costs and prevalence of prior authorization or quantity limit policies between PDPs and MADPs for oral ondansetron, an essential and widely used antiemetic for patients with cancer. Methods: We used 2023 Q3 MA and PDP data from the Center for Medicare and Medicaid Services, excluding employer-sponsored and Supplemental Need Plans (including dual-eligible plans) and plans with &lt; 10 enrollees. We focused on the four most common generic ondansetron forms: 4mg and 8mg tablets, and 4mg and 8mg orally disintegrating tablets (ODT). To compare medication quantities, we calculated the median (IQR) cost of 30-day supply (90 dosage units), defining plan-level price as the average unit cost for each formulation. Price benchmarks were defined using Mark Cuban Cost-plus Drug Company cash prices, which reflect fixed markup to negotiated wholesale prices. T-test and Chi-square tests were used for comparison. Results: Across 813 PDPs and 3512 MADPs, MAPDs had lower median costs for a 30-day supply of ondansetron than PDP plans (4mg tab: $16.1 vs $29.2; 4mg ODT: $38.0 vs $56.4; 8mg tab: $24.7 vs $35.6; 8mg ODT: $37.2 vs $54.4, all p &lt; 0.01). Median costs for both PDPs and MAPDs were higher than benchmarks (66-155% across formulations; all p &lt; 0.01). PDPs and MAPDs had similarly high prior authorization rates (83.6% vs 83.4%, p = 0.89), but MAPDs used quantity limits more frequently (22.5% vs 16.5%, p &lt; 0.01). There was little variation in prior authorization and quantity limit policies across formulations. Conclusions: Ondansetron costs in both PDPs and MAPDs were higher than benchmarks. Compared to PDPs, MAPDs offered ondansetron at lower costs but used policies creating access barriers for patients either at similar (prior authorization) or higher (quantity limit) frequency, burdening patients, physicians, health systems, and pharmacies. [Table: see text]

Quality assessment of oral antimalarial and antiretroviral medicines used by public health systems in Sahel countries

Malaria and Human Immunodeficiency Virus infections are among the top 10 causes of death in low income countries. Furthermore, many medicines used in these treatment areas are substandard, which contributes to the high death rate. Using a monitoring system to identify substandard and falsified medicines, the study aims to evaluate the quality of antimalarial and antiretroviral medicines in Sahel countries, assessing site conditions, compliance of medicines with pharmacopoeia tests, formulation equivalence with a reference medicine, and the influence of climate on quality attributes. Ultra Performance Liquid Chromatography methods for eight active pharmaceutical ingredients were validated following the International Conference for Harmonization guideline for its detection and quantification. Quality control consists of visual inspections to detect any misinformation or imperfections and pharmacopeial testing to determine the quality of pharmaceutical products. Medicines which complied with uniformity dosage units and dissolution tests were stored under accelerated conditions for 6 months. Artemether/Lumefantrine and Lopinavir/Ritonavir formulations failed uniformity dosage units and disintegration tests respectively, detecting a total of 28.6% substandard medicines. After 6 months stored under accelerated conditions (40 °C // 75% relative humidity) simulating climatic conditions in Sahel countries, some medicines failed pharmacopeia tests. It demonstrated the influence of these two factors in their quality attributes. This study emphasizes the need of certified quality control laboratories as well as the need for regulatory systems to maintain standards in pharmaceutical manufacturing and distribution in these countries, especially when medicines are transported to rural areas where these climatic conditions are harsher.

Review Article A Detailed Study on Disintegrating Agents and an Overview on Oral Disintegration Tablet

Nowadays, the administration of drugs through the oral route is becoming less common, accounting for only about 75% of all drug administrations compared to other routes. A new type of dosage form called oral disintegrating tablets has gained popularity in recent decades due to their rapid disintegration and dissolution. These tablets disintegrate in the mouth within seconds (25-40 seconds) without the need for water, as the oral mucosa alone is sufficient for the tablet to dissolve. The selection of a suitable disintegrating agent is crucial to achieve optimal bioavailability. A preparation may contain one or multiple disintegrating agents to ensure maximum disintegration and bioavailability. These tablets are also known as Oro disintegration tablets. Disintegrating agents are rarely used in solid unit dosage forms, typically comprising only 1-10% of the total dosage unit. The use of super disintegrates in these tablets enhances the drug's efficacy by promoting rapid dissolution. Various disintegrating agents, super disintegrates, and excipients are employed in the formulation of oral disintegrating tablets. This review article provides an overview of different types of disintegrates, including natural, polymer, and synthetic ones, as well as formulation methods, applications, and various parameters of oral disintegrating tablets. These tablets are particularly well-liked by pediatric patients and those who prefer generic medications. Oral disintegrating tablets are highly preferred in the treatment of dysphagia and oral disorders among patients. Keywords: - Oral disintegrating tablets, Oro disintegrating tablets, Disintegrates, Super disintegrates and Fast dissolution tablet.

Revolutionizing Apixaban Release: Exploring Wet Granulation and Superdisintegrant Synergy for Improved Delivery Profiles

The aim of the present research was to formulate and evaluate immediate release tablet of apixaban. In this research study, we are formulating apixaban by wet granulation method. Previously research has been conducted based on dry granulation and direct compression methods.&#x0D; The proposed wet granulation method has several advantages in terms of feasibility and cost effectiveness. The present formulation comprises of comparative evaluation between disintegrants such as sodium starch glycolate (SSG), and croscarmellose sodium (CCS), among which CCS was found to have optimum results. Superdisintegrants, are compounds that, as their name implies, are superior to disintegrants and that facilitate or enhance the disintegration time even at low levels, usually 1-10% by weight relative to the total weight of the dosage unit. These are used to boost the potency of the solid dosage form.

Revolutionizing Three-Dimensional Printing: Enhancing Quality Assurance and Point-of-Care Integration through Instrumentation.

Three-dimensional printing in the field of additive manufacturing shows potential for customized medicines and solving gaps in paediatric formulations. Despite successful clinical trials, 3D printing use in pharmaceutical point-of-care is limited by regulatory loopholes and a lack of Pharmacopoeia guidelines to ensure quality. Semi-solid extrusion is a 3D printing technology that stands out for its versatility, but understanding the fluid dynamics of the semi-solid mass is critical. The aim of this research is to look into the advantages of instrumenting a 3D printer with a semi-solid extrusion motor-driven printhead, which is able to record the printing pressure over time, for in situ characterization of the semi-solid mass and quality evaluation of dosage forms. Four formulations using hydrochlorothiazide as the active pharmaceutical ingredient and several excipients were used. Their flow properties were studied at different printing speeds and temperatures using traditional techniques (rheometer and Texture Analyzer) and the proposed semi-solid extrusion motor-driven printhead incorporated into a printing platform. In addition, the influence of printing speed in the printing process was also evaluated by the study of printing pressure and printlet quality. The results demonstrated the similarities between the use of a Texture Analyzer and the semi-solid extrusion motor-driven. However, the latter enables temperature selection and printing speed in accordance with the printing process which are critical printing parameters. In addition, due to the incorporation of a sensor, it was possible to conclude, for the first time, that there is a link between changes in essential printing parameters like printing speed or formulations and variations in printing pressure and printlet quality attributes such as the energy require to obtain a single dosage unit, weight or diameter. This breakthrough holds a lot of potential for assuring the quality of 3D printing dosage forms and paving the way for their future incorporation into point-of-care settings.

Optimization of ticagrelor tablet for gastro-retentive drug delivery using full factorial design

Purpose: To identify the optimized region of formulation using quality by design for developing ticagrelor gastro-retentive (GR) tablets. &#x0D; Methods: A 23 + 3 full factorial design of experiments study was used to identify three factors (polyethylene oxide (PEO), compression, and volume of granulating fluid) involved in the wet granulation and compression process of ticagrelor GR tablets. Hardness, friability, content, dosage unit uniformity, and pH 1.2 dissolution rate (at 4, 8, and 12 h) were evaluated as critical quality attributes via analysis of variance using Design Expert software. &#x0D; Results: All seven models were significantly influenced based on analysis of variance results (p &lt; 0.05). Hardness and friability were significantly affected by compression (p &lt; 0.0001). Content uniformity was significantly affected by the interaction between compression and granulating water volume for wet granulation (p &lt; 0.05), and dosage unit uniformity was significantly affected by the volume of granulating fluid for wet granulation (p &lt; 0.05). However, all results were within acceptable ranges. Polyethylene oxide (PEO) (4 h, p &lt; 0.05; 8 h, p &lt; 0.05; 12 h, p &lt; 0.05) and compression (4 h, p &lt; 0.05; 8 h, p &lt; 0.05; 12 h, p &lt; 0.05) had negative effect on pH 1.2 dissolution rate. &#x0D; Conclusion: Design of experiment (DoE) approach has been used to optimize region of PEO, compression, and volume of granulating fluid for formulation development. This outcome is expected to be a basis for further research to develop TCG GR tablets on a large production scale.

(253) Use of Online Pharmacy Tools May Lead to Significantly Reduced National Expenditures on Vaginal Estrogen

Abstract Introduction High medication costs for vaginal estrogen may create a barrier for patients seeking treatment for numerous urinary and vaginal symptoms and lead to poor medication adherence. The Mark Cuban Cost Plus Drug Company (CPD) and GoodRx tools offer patients a method to purchase prescription medications at a discount, which may lead to improved medication adherence and decreased national expenditures on such medications. Objective To compare the pricing of vaginal estrogen as advertised by retail pharmacies, Medicare, and discount listings through CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain listed retail and discounted prices for Estrace (topical), Vagifem (tablet), and Premarin (topical). GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD and/or GoodRx. Results Average spending per dosage unit for Estrace, Vagifem, and Premarin was lesser when discount tools were used (0.50 $/adu, 3.75 $/adu, and 4.30 $/adu respectively), compared to Medicare pricing (6.14 $/adu, 20.95 $/adu, and 10.10 $/adu respectively) or retail pricing (3.14 $/adu, 10.19 $/adu, and 5.43 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $64.2M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual national saving of $39.2M. Conclusions The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications.

Application of the variability budget approach to the Dissolution test

The aim. This study aimed to evaluate the completeness of our knowledge about the sources of variation in the Dissolution test with 100 % release by compiling a variability budget.&#x0D; Materials and methods. The study was performed on 500 mg metformin tablets, using pharmacopoeial quality reagents, State Pharmacopoeia of Ukraine (SPhU) Metformin HCl reference standard, Pharmatest DT70 Dissolution apparatus, Perkin Elmer Lambda 35 spectrophotometer, Mettler Toledo XP 204 analytical balance, and ISO class A volumetric glassware. The SPhU metrological approach was employed.&#x0D; Results and discussion. The variability budget was compiled based on the comparison of uncertainty estimates obtained from the requirements for maximum permissible variation in normal analytical practice (UNAP, bottom-up estimation) and experimental data (Uexp). This involved characterizing Metformin content in tablets using the Uniformity of Dosage Units (UDU) test as an independent method. The 100 % release of Metformin in the Dissolution test (infinity point) was proved by increasing the dissolution time. Having optimized Dissolution and UDU analytical procedures for variability budget compiling, we achieved insignificance of Uexp compared to the target uncertainty (Utg) for the Dissolution test in compliance testing. The differences in UDU and Dissolution mean results did not exceed UNAP for the release time of 45 and 60 min, i.e. uncertainty budget was proven. Uexp for the Dissolution test indicated the presence of an unknown statistically significant source of random variation, which, however, was less than Utg; therefore, the procedure is suitable for compliance testing.&#x0D; Conclusion. Experimental results confirmed the completeness of our knowledge about sources of variation (absence of bias) for the Dissolution test with 100 % release. An essential condition for compiling the budget was the optimization of uncertainty of analytical procedures. For UDU, all significant sources of variation were within the expected range. Yet, there is a need for additional research to identify and manage an unknown source of practically significant random variation for the Dissolution test

A101 TRENDS IN MEDICAID SPENDING FOR HEPATITIS C TREATMENT FROM 2012-2021

Abstract Background Hepatitis C virus (HCV) infection is a pervasive disease that reduces quality and quantity of life. Medicaid is the largest health insurance program in the United States that provides coverage to individuals with low income including children, pregnant individuals, and people with disabilities. Due to the impact of HCV on individuals and the world goal for elimination of HCV by 2030, an analysis of healthcare costs attributed to hepatitis C medications is imperative to guide further policy and coverage changes. Aims To analyze Medicaid spending and utilization for hepatitis C treatment from 2012 to 2021 and provide a reflection on the impact it has on healthcare costs in the USA. Methods The Centers for Medicare &amp; Medicaid Services public database was accessed to obtain Medicaid spending on Hepatitis C medications from 2012-2021. Data extracted included brand and generic drugs to treat HCV, total annual spending, total dosage units prescribed, total number of claims, and average spending per dosage unit and claim. Microsoft Excel was used for data analysis and creation of graphs. Results A total of 20 oral medications were included in this study. Total spending on all medications per year increased from $184 million in 2012 and peaked in 2016 at $3.3 billion. In 2021, the highest amount of Medicaid spending was on Mavyret ($658 million) followed by generic sofosbuvir-velpatasvir ($389 million) and Epclusa ($262 million). The total number of claims decreased from 135,542 in 2012 to 121,101 in 2021 with a peak in 2016 at 159,826. During the same time, the average spending per claim increased from 2012 ($6,518) to 2021 ($146,792). In 2021, the highest average spending per claim was seen with Harvoni ($30,941) followed by Sovaldi ($27,247), Vosevi ($23,877), and Epclusa ($22,917). In the same year, Mavyret had the greatest number of claims at 51,500 followed by generic sofosbuvir-velpatasvir (50,115), Epclusa (11,437), and Vosevi (2,177). Conclusions Despite the number of claims declining from 2012 to 2021, the average spending has increased due to the significant cost of HCV medications on Medicaid spending. The highest spending was noted to be with originator medications while generic formulations had the highest number of claims. Understanding the trends in spending on HCV medications can help guide insurance coverage changes for those depending on Medicaid. Lastly, shifting policies towards increased use of generic medications can help with increasing access and reducing costs to the population. Figure 1. Total annual spending per year in billions ($ USD, blue bars) and total number of claims (orange line) per year from 2012 to 2021. Funding Agencies None

Strategies to enhance treatment fidelity and music-based intervention reporting in dementia research.

Creative solutions are needed to address the well-being of the growing number of individuals living with dementia. Music-based interventions (MBIs) are promising and can be cost-effective; however, empirical evidence for MBIs is limited and published findings have not been widely translated into practice. Here, we describe how we implemented strategies to enhance rigor in a randomized clinical trial of an MBI for persons with dementia. We examined the impact of a singing-based MBI on feelings, emotions, and social engagement, relative to a non-music treatment (verbal discussion), delivered in small group format (25 minutes, 3 times/week for 2 weeks). We implemented National Institutes of Health Behavior Change Consortium strategies regarding: (i) design, (ii) interventionist training, (iii) treatment delivery, (iv) treatment receipt, and (v) treatment skills enactment. We applied the MBI Reporting Criteria including: (i) theoretical framework, (ii) musical content, (iii) dosage, (iv) interventionist, (v) treatment fidelity, (vi) setting, and (vii) delivery unit. We analyzed data with a separate linear mixed model for each dependent variable. 32 older adults with dementia (65-97 years) participated. The MBI yielded significant positive effects on all measured outcomes (all p's < .05). Application of established guidelines enhanced methodological rigor and MBI reproducibility. To support translation of research into practice, clinicians should understand how to implement an MBI reported in research. Our study illustrates practical steps to address the need for improved MBI research in persons with dementia and can provide a model for others to enhance evidence-based practice with this population.

(317) Significant Cost Savings for Erectile Dysfunction Medications are Available Using Discount Online Pharmacies Compared to Medicare

Abstract Introduction The Mark Cuban Cost Plus Drug Company (CPD) is an online retailer launched in January 2022 that sells generic prescription medications directly to consumers at cost of ingredients and manufacturing plus a fixed 15% margin in addition to a small pharmacy dispensing fee and shipping fee. GoodRx is an online tool which offers coupons redeemable at pharmacies for discounts on prescription medications. The combination of these two tools offers physicians a way to provide prescription medications to patients at lower costs, which may lead to improved medication adherence and lower medication expenditures nationally. Objective To compare the cost of various erectile dysfunction medications when purchased through retail pharmacies, reimbursed through Medicare, or obtained utilizing CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain average retail and discounted prices for generic sildenafil, tadalafil, and vardenafil. GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD or GoodRx. Results Average spending per dosage unit for sildenafil, tadalafil, and vardenafil was less when GoodRx or CPD were used (0.28 $/adu, 0.31 $/adu, and 6.17 $/adu respectively), compared to Medicare pricing (2.14 $/adu, 8.08 $/adu, and 27.84 $/adu respectively) or retail pricing (0.52 $/adu, 2.82 $/adu, and 8.35 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $149M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual nation saving of $40M. Conclusions The utilization of CPD and GoodRx in the prescription of common erectile dysfunction medications may lead to significant reductions in pricing compared to retail and Medicare estimates. Knowledge of these prescription tools may lead to significant reductions in national expenditures on medications and decreased cost burden for patients seeking treatment. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.

(003) Use of Online Pharmacy Tools May Lead to Significantly Reduced National Expenditures on Vaginal Estrogen

Abstract Introduction High medication costs for vaginal estrogen may create a barrier for patients seeking treatment for numerous urinary and vaginal symptoms and lead to poor medication adherence. The Mark Cuban Cost Plus Drug Company (CPD) and GoodRx tools offer patients a method to purchase prescription medications at a discount, which may lead to improved medication adherence and decreased national expenditures on such medications. Objective To compare the pricing of vaginal estrogen as advertised by retail pharmacies, Medicare, and discount listings through CPD and GoodRx. Methods A review of publicly available data from CPD and GoodRx was performed to obtain listed retail and discounted prices for Estrace (topical), Vagifem (tablet), and Premarin (topical). GoodRx prices were obtained using prices from Costco, CVS, Walgreens, and Walmart pharmacies in the most from populous zip code from each of the 3 most populous U.S. states: California, New York, and Texas. Prices were adjusted to account for dosage and prescribed quantity to estimate an average cost per dosage unit ($/adu). The Medicare Part D Drug Spending and Utilization data from 2021 were used to report the average spending per dosage unit and total expenditure for each of the listed medications. These data were compared to create an estimate of average national savings after use of CPD and/or GoodRx. Results Average spending per dosage unit for Estrace, Vagifem, and Premarin was lesser when discount tools were used (0.50 $/adu, 3.75 $/adu, and 4.30 $/adu respectively), compared to Medicare pricing (6.14 $/adu, 20.95 $/adu, and 10.10 $/adu respectively) or retail pricing (3.14 $/adu, 10.19 $/adu, and 5.43 $/adu respectively). When adjusted for total dosage units, use of CPD over Medicare pricing for the three medications would result in a combined annual national saving of $64.2M. Use of either CPD or GoodRx compared to retail pricing would similarly result in a combined annual national saving of $39.2M. Conclusions The utilization of CPD and GoodRx in the prescription of vaginal estrogen led to a substantial national average cost savings when compared to retail and Medicare pricing. CPD and GoodRx may offer a way to decrease the cost burden for patients seeking treatment for urinary and vaginal symptoms and significantly reduce national expenditures on medications. Disclosure Any of the authors act as a consultant, employee or shareholder of an industry for: Advisory board and speaker for Coloplast; consultant for Cynosure; advisory board and speaker for Halozyme; intellectual property with Masimo; advisory board for Promescent; consultant for Sprout; advisory board for Xialla.