Development and Validation of High-Performance Liquid Chromatography Method for the Quantification of Remdesivir in Intravenous Dosage Form.

Corona virus disease 2019 (COVID-19) has posed a mounting threat to public health with worldwide outbreak caused by a novel virus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Recently, remdesivir (RDV) has been approved by Food and Drug Administration (FDA) for treating COVID-19 patients ≥12 years old requiring hospitalization. To the best of our knowledge, a simple method to estimate RDV in the pharmaceutical formulations using high-performance liquid chromatography (HPLC) is still unexplored, highlighting the need for a precise analytical method for its quantification. The prime purpose of the current investigation was to develop and validate a well-grounded HPLC method for quantification of RDV in pharmaceutical formulations. The best chromatogram was obtained by means of an Inertsil ODS-3V column using a mobile phase of milli-Q water modified to pH 3.0 with o-phosphoric acid and acetonitrile (50:50, % v/v) at a flow rate of 1.2 mL/min and wavelength of detector set at 246 nm with retention time being achieved at 6.0 min. The method was validated following International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2 (R1) guidelines for various parameters such as specificity and selectivity, system suitability, linearity, precision, accuracy, limits of detection and quantification, and robustness. The method developed for the quantification of RDV was found to be linear in the concentration range of 25-2,500 ng/mL with limit of detection and limit of quantification of 1.95 and 6.49 ng/mL, respectively. Assay value of 102% ± 1% was achieved for marketed injectable dosage form when estimated by the validated method. Therefore, in this study a simple, rapid, sensitive, selective, accurate, precise, and robust analytical method was developed and validated for the quantification of RDV using HPLC. The established method was successfully employed for quantification of RDV in marketed pharmaceutical formulation.

Approach to Establishment of Control Strategy for Oral Solid Dosage Forms Using Continuous Manufacturing.

As a result of the research activities of the Japan Agency for Medical Research and Development (AMED), this document aims to show an approach to establishing control strategy for continuous manufacturing of oral solid dosage forms. The methods of drug development, technology transfer, process control, and quality control used in the current commercial batch manufacturing would be effective also in continuous manufacturing, while there are differences in the process development using continuous manufacturing and batch manufacturing. This document introduces an example of the way of thinking for establishing a control strategy for continuous manufacturing processes.

Impresión 3D de medicamentos / 3D Printing of medicines

La industria farmacéutica está en continua búsqueda de nuevas tecnologías que permitan mejorar las formas de dosificación de las que se dispone, siendo uno de los objetivos el aumento de la adherencia a los tratamientos por parte de los pacientes. En este sentido, la impresión en 3 dimensiones (3DP) es una emergente técnica de fabricación aditiva que ha comenzado a abarcar muchos sectores industriales e influir directa e indirectamente en la calidad de vida de los individuos. Tanto es así, que la 3DP se postula como una de las técnicas que podría contribuir a que se produzca un gran cambio en el sector farmacéutico, permitiendo la personalización de los tratamientos de los pacientes, mejorando la biodisponibilidad de fármacos que presentan problemas de disolución o combinando toda la medicación de un paciente en una sola forma farmacéutica de toma diaria (polypill), entre otros. Esta nueva técnica de producción va a diferir enormemente de las clásicas formas de fabricación farmacéuticas y, en los próximos años puede suponer una transformación revolucionaria en la práctica farmacéutica

The pharmaceutical industry is continually searching for new technologies to improve the characteristics of current medicines. One of the objectives is the increase of adherence to the treatments by patients. Simultaneously, 3-dimensional printing (3DP) is an emerging additive technique that is reaching many sectors of industry and influencing directly and indirectly the quality of life of patients. In this sense, 3DP postulates to be one of the technologies that contribute to the pharmaceutical development, allowing the personalized medicine in patients, improving the bioavailability of drugs with dissolution problems or combining all the medication of the patients in a single tablet (polypill), among others. This new technique will differ greatly from the traditional pharmaceutical manufacturing and in the coming years it may involve a revolutionary transformation in pharmaceutical practice

Evaluation of traditional initial vancomycin dosing versus utilizing an electronic AUC/MIC dosing program

BACKGROUND: Area under the curve to minimum inhibitory concentration (AUC/MIC) has been recommended by the 2020 updated vancomycin guidelines for dosing vancomycin for both efficacy and safety. Previously, AUC/MIC has been cumbersome to calculate so surrogate trough concentrations of 15-20 mg/dL were utilized. However, trough-based dosing is not a sufficient surrogate as AUC/MIC targets of 400-600 can usually be reached without achieving troughs of 15-20 mg/dL. Targeting higher trough levels may also lead to adverse events including acute kidney injury (AKI) and nephrotoxicity. OBJECTIVE: To compare the mean total first day vancomycin dose in traditional trough-based dosing versus dosing recommended by an AUC/MIC dosing program. METHODS: Adult inpatients who received at least 24 hours of IV vancomycin treatment were included in this single-center, retrospective cohort study. The primary endpoint was difference in mean total first day vancomycin dose in milligrams (mg) received between patients' traditional trough-based dosing and recommended dose via AUC/MIC electronic dosing calculator. Patients served as their own control by analyzing both actual dose received and dose recommended by the electronic AUC/MIC program. Rates of vancomycin induced adverse events, including acute kidney injury, elevated steady-state trough concentrations, and Red Man's syndrome were also compared between patients who received doses consistent with the AUC/MIC dosing recommendation versus those who did not. RESULTS: 264 patients were included in this study. Initial 24-hour vancomycin exposure was significantly lower with the recommended AUC/MIC dose versus the dose received (2380.7; SD 966.6 mg vs 2649.6; SD 831.8 mg, [95% CI 114.7:423.1] p = 0.0007). CONCLUSIONS: Utilizing an electronic AUC/MIC vancomycin dosing calculator would result in lower total first day vancomycin doses

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Relative Bioavailability of Enalapril Administered as Orodispersible Minitablets in Healthy Adults.

The angiotensin-converting enzyme inhibitor enalapril is commonly used to treat chronic heart failure in children. Because some children are unable to swallow capsules or tablets, a new, age-appropriate, orodispersible minitablet (ODMT) containing 1 mg of enalapril was developed within the EU-funded LENA (Labeling of Enalapril from Neonates up to Adolescents) consortium. In order to support the clinical evaluation of this new formulation in children, a relative bioavailability study was performed in healthy adults, comparing the bioavailability of enalapril in the ODMT with that of a reference product (RP) Renitec, a registered standard enalapril tablet formulation. In this open-label, randomized 3-way crossover study, 24 healthy subjects received a 10-mg enalapril dose administered as (1) 2 × 5-mg tablets of the RP swallowed with water, (2) 10 × 1-mg ODMT swallowed with water, and (3) 10 × 1 mg ODMT dispersed on the tongue. When the relative bioavailability of the ODMT formulation swallowed with water was compared with that of the RP, the estimated 90%CIs for the ratio of area under the concentration-time curve (AUC0-∞ ) and or peak concentration (Cmax ) of enalapril were 92.34% to 106.49% and 91.28% to 115.72%, respectively, which are within the accepted bioequivalence limits of 80% to 125%. Following dispersion of the ODMT in the mouth, a slightly higher Cmax for enalapril was observed as compared with the RP with an upper 90%CI of 127.57%, slightly exceeding the bioequivalence limit. Taken together, it was demonstrated that the method of administration of the ODMT, swallowed or dispersed, did not significantly affect the bioavailability of enalapril.

Unmet Quality Needs in Oral Drug Delivery: Contrasts of Drug Content and Uniformity on Distinct Approaches for Achieving Individual Dosing.

Individualized dosing is often required in pharmacotherapy, particularly for pediatric and geriatric patients and adjustment of drugs that demand dose adaptation. This study aimed to evaluate critical quality attributes (CQAs) of doses obtained by distinct approaches for achieving individual dosing. Approaches were evaluated as follows: subdivision of tablets by splitter and hand (haloperidol) and delivery by plastic dropper bottle (haloperidol), glass dropper bottle (clonazepam), dosing cup (sodium valproate), and dosing syringe (carbamazepine), including brand name, generic, and similar marketed products. Measuring devices were packaged with their respective product. Drug content uniformity was assessed to each substance according to pharmacopeial methods. Tablets subdivided by splitter had the poorest performance among all approaches, in which doses ranged around 60% of the labeled amount (Acceptance Value = 58.1 and RSD = 23.2%). The greatest performances were observed for the dosing syringe which fulfilled all the requirements for dose precision and for the glass dropper bottle. There were significant differences in dose delivery between manufacturers of the same medicine when measuring the same volume or number of drops. High drug content variability is extremely harmful to pharmacotherapy and may result in therapeutic failure or toxicity. It is crucial that measuring devices and scoring of tablets be checked for functionality and standardized for different manufacturers of the same medicine. Part of the approaches for achieving individual dosing did not meet the quality needs for drug content and uniformity. Yet, our findings show that more accurate and precise dosing can be accessed when using the dosing syringe and glass dropper bottle.

Power of the Dissolution Test in Distinguishing a Change in Dosage Form Critical Quality Attributes.

For a dissolution method to be considered relevant to in vivo performance, the dissolution data profiles should show discrimination or meaningful change when there is a change in critical material attributes (CMAs) and critical product properties (CPPs). The dissolution test has been shown repeatedly to have the power to distinguish between significant changes in active pharmaceutical ingredient (API), formulation, and process that relate to the release mechanism of the in vivo performance. Examples will be discussed in the literature where the effects of formulation, drug substance, and manufacturing variables have been measured by dissolution testing. There will be a suggested plan on how to develop and challenge a discriminating method that may be utilized for regulatory purposes. A brief review of other challenges and considerations regarding discriminatory dissolution testing is presented.

Evaluation of a vancomycin dosing nomogram in obese patients weighing at least 100 kilograms

Background: There remains variability in both practice and evidence related to optimal initial empiric dosing strategies for vancomycin. Objective: Our primary objective was to describe the percentage of obese patients receiving vancomycin doses consistent with nomogram recommendations achieving targeted initial steady-state serum vancomycin concentrations. Secondary objectives were to describe the primary endpoint in subgroups based on patient weight and estimated creatinine clearance, to describe the rate of supratherapeutic vancomycin accumulation following an initial therapeutic trough concentration, and to describe the rate of vancomycin-related adverse events. Methods: This single-center, IRB-approved, retrospective cohort included adult patients ≥ 100 kilograms total body weight with a body mass index (BMI) >30 kilograms/m2 who received a stable nomogram-based vancomycin regimen and had at least one steady-state vancomycin trough concentration. Data collected included vancomycin regimens and concentrations, vancomycin indication, serum creatinine, and vancomycin-related adverse events. Patients were divided into two cohorts by goal trough concentration: 10-15 mcg/mL and 15-20 mcg/mL. Results: Of 325 patients screened, 85 were included. Goal steady-state concentrations were reached in 42/85 (49.4%) of total patients. Conclusions: Achievement of initial steady-state vancomycin serum concentrations in the present study (approximately 50%) was consistent with the use of published vancomycin dosing nomograms

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Drug Quality in South Africa: A Field Test.

To assess drug quality and pharmaceutical care in South Africa, "mystery" (i.e., anonymous) customers collected 316 samples from July to September 2016. Solid dosage forms containing amoxicillin alone or in combination with clavulanic acid as well as analgesics containing paracetamol alone or in combination with other drugs were sampled in a randomized fashion from the formal market (pharmacies) and by convenient sampling from the informal market. Visual inspection, uniformity of dosage units, and dissolution testing were performed to evaluate adherence to pharmacopoeial quality standards and to identify counterfeit, degraded, or substandard drugs. Although no counterfeited products were identified, only 55.4% (173/312) of samples were able to fulfill all pharmacopeial requirements for quality. Most of the 139 samples that failed were unable to pass the visual inspection due to inappropriate labeling and packaging. In addition, several substandard products were identified: 17 (5.4%) samples failed dissolution testing and 15 (4.8%) failed the content uniformity test. To improve drug quality and the quality of pharmaceutical care, better education of pharmaceutical professionals and monitoring of the pharmaceutical supply chain in South Africa are needed. Further field studies are necessary to evaluate risks and quality issues for other drug classes and distribution channels.

Continuous Manufacturing in Pharmaceutical Process Development and Manufacturing.

The pharmaceutical industry has found new applications for the use of continuous processing for the manufacture of new therapies currently in development. The transformation has been encouraged by regulatory bodies as well as driven by cost reduction, decreased development cycles, access to new chemistries not practical in batch, improved safety, flexible manufacturing platforms, and improved product quality assurance. The transformation from batch to continuous manufacturing processing is the focus of this review. The review is limited to small, chemically synthesized organic molecules and encompasses the manufacture of both active pharmaceutical ingredients (APIs) and the subsequent drug product. Continuous drug product is currently used in approved processes. A few examples of production of APIs under current good manufacturing practice conditions using continuous processing steps have been published in the past five years, but they are lagging behind continuous drug product with respect to regulatory filings.

Different insulin concentrations in resuspended vs. unsuspended NPH insulin: Practical aspects of subcutaneous injection in patients with diabetes.

AIMS: This study measured the insulin concentration (Ins[C]) of NPH insulin in vials and cartridges from different companies after either resuspension (R+) or not (R-; in the clear/cloudy phases of unsuspended NPH). METHODS: Measurements included Ins[C] in NPH(R+) and in the clear/cloudy phases of NPH(R-), and the time needed to resuspend NPH and time for NPH(R+) to separate again into clear/cloudy parts. RESULTS: In vials of NPH(R+) (assumed to be 100%), Ins[C] in the clear phase of NPH(R-) was<1%, but 230±41% and 234±54% in the cloudy phases of Novo Nordisk and Eli Lilly NPH, respectively. Likewise, in pen cartridges, Ins[C] in the clear phase of NPH(R-) was<1%, but 182±33%, 204±22% and 229±62% in the cloudy phases of Novo, Lilly and Sanofi NPH. Time needed to resuspend NPH (spent in tipping) in vials was brief with both Novo (5±1s) and Lilly NPH (6±1s), but longer with all pen cartridges (50±8s, 40±6s and 30±4s from Novo, Lilly and Sanofi, respectively; P=0.022). Time required for 50% separation into cloudy and clear parts of NPH was longer with Novo (60±7min) vs. Lilly (18±3min) in vials (P=0.021), and affected by temperature, but not by the different diameter sizes of the vials. With pen cartridges, separation into clear and cloudy parts was significantly faster than in vials (P<0.01). CONCLUSION: Ins[C] in NPH preparations varies depending on their resuspension or not. Thus, subcutaneous injection of the same number of units of NPH in patients with diabetes may deliver different amounts of insulin depending on its prior NPH resuspension.

Orodispersible dosage forms: biopharmaceutical improvements and regulatory requirements.

Orodispersible dosage forms have a growing presence in the pharmaceutical market because their administration can improve the bioavailability of some drugs and their prescription can ameliorate patient adherence and/or compliance. Here, we review the main features of orodispersible tablets, including oral lyophilisates, and orodispersible films along with their main production technologies. We summarize the bioavailability data and critically discussed their potential to improve patient adherence and/or compliance. We revisit this information in light of both the European Union (EU) and US regulatory frameworks, focusing on the differences in the definitions of such dosage forms and the requirements for marketing authorization.

Bleomicina, cuando los miligramos no hacen referencia al peso / Bleomycin, when miligrams do not refer to weight

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A rapid validated UV-HPLC method for the simultaneous determination of the antiretroviral compounds darunavir and raltegravir in their dosage form / Determinación simultánea de los compuestos antirretrovirales darunavir y raltegravir en su forma farmacéutica mediante un método rápido y validado de UV-HPLC

Introduction. A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form. Material and methods. The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5-100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15x0.4.6 cm) column at 35ºC. The selected wavelength was 254 nm. The mobile phase was a mixture of 0.037 M sodium dihydrogen phosphate buffer, acetonitrile and methanol (40:50:10, v/v/v) at a flow rate of 2.0 mL/min Nevirapine (50 mg/L) was used as internal standard. Results. Accuracy, intraday repeatability (n = 5), and inter-day precision (n = 3) were found to be satisfactory, being the accuracy from -4.33 to 3.88% and precisions were intra-day and interday, 0.25% and 4.42% respectively in case of darunavir. Raltegravir intraday and interday precisions lower of 1.01 and 2.36%, respectively and accuracy values bet from -4.02 to 1.06%. Conclusions. Determination of the darunavir and raltegravir in their dosage form was done with a maximum deviation of 4%. This analytical method is rapid, easily implantable and offers good results (AU)

Introducción. Un método rápido, sencillo y sensible de cromatografía líquida de alto rendimiento (HPLC) con detección ultravioleta ha sido desarrollado para la cuantificación simultánea de darunavir y raltegravir en su forma farmacéutica. Material y métodos. La determinación se llevó a cabo empleando una columna Tracer Excel 120 ODSB (15x0.4.6 cm) C18 a 35 ºC. La longitud de onda empleada fue de 254 nm. La fase móvil fue una mezcla de una disolución tampón dihidrógeno fosfato de sodio 0,037 M, acetonitrilo y metanol (40:50:10, v/v/v) con un flujo de 2,0 mL/min. El fármaco nevirapina (50 mg/L) fue usado como patrón interno. Resultados. El ensayo realiza la medida de ambos fármacos con una curva de calibración lineal (R2= 0,999) en un rango de concentración de 5 a 100 mg/L. Los valores de exactitud, repetibilidad intradía (n = 5) e interdía (n = 3) han resultado satisfactorios, encontrándose los valores de exactitud entre -4.33 y 3.88%, y las precisiones intradía e interdía, 0,25% y 4,42%, respectivamente en caso de darunavir. En el caso del raltegravir, las precisiones intradía e interdía fueron de 1,01 y 2,36%, respectivamente y para la exactitud se obtuvieron valores entre -4,02 y 1,06%. Conclusiones. La determinación de darunavir y raltegravir en su forma farmacéutica fue llevada a cabo observándose una desviación máxima del 4%. El método es rápido, fácilmente implantable y ofrece buenos resultados (AU)

Novedades en patología infecciosa para un pediatra de Atención Primaria / Novelties on infectious pathology for a Primary Care pediatrician

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Encouraging pharmacist intervention and standardization of labeling and dispensing of oral liquid medications.

OBJECTIVES: To initiate a call to action for community pharmacists and key-pharmacy stakeholders in the standardization of oral-liquid dosage forms. DATA SOURCES: Not applicable. SUMMARY: Unintentional overdose of medication due to administration error results in thousands of pediatric hospitalizations yearly. A lack of prescription and dosage device standardization pertaining to oral-liquid medications continue to be a public health hazard. Multiple professional organizations have publicly endorsed the standardization of oral liquid dosage forms. Universal adoption will not be achieved until key-pharmacy stakeholders encourage their pharmacists to use best practices when verifying and preparing prescription medication. Specifically, these practices should include immediate conversion of prescriptions containing non-metric volumes into metric volumes, providing appropriate sized oral dosing syringes for all oral liquid prescriptions, writing dosing directions in the safest format, and counseling patients and caretakers of proper medication administration. CONCLUSION: Community pharmacists are uniquely positioned to lead the universal adoption of these best practices to ensure proper oral-liquid dosing administration for all patients.

Comparison of two concentrations of bupivacaine by continuous paravertebral infusion after thoracotomy with pulmonary resection: a double-blind, randomized clinical trial

Background and objectives: Post-thoracotomy pain management should be based on a multimodal approach that includes continuous regional analgesia. The objective of this study was to compare the analgesic efficacy of two concentrations of bupivacaine (0.2 % and 0.3 %) through a paravertebral catheter, both group plus fentanyl 2 mcg/ml. Methods: We conducted a randomized double-blind clinical trial to compare these two concentrations in patients undergoing pulmonary resection by thoracotomy in Donostia University Hospital between November 2010 and May 2011 (n = 59). The paravertebral catheter was placed prior to the surgical intervention, with the patient awake and sitting upright. Data were analyzed on an intention-to-treat basis. The Chi-squared test was used for qualitative variables and Student’s t-tests or Mann-Whitney-Wilcoxon tests for quantitative variables, depending on the distribution of the variables. Statistical analysis was performed using IBM SPSS software (Version 17). Results: We did not find statistically significant differences in postoperative pulmonary function (p = 0.49), self-perceived pain (VAS; p = 0.28) or cumulative morphine consumption (p = 0.101) in the two groups. We observed adverse effects in 8 patients in group 1 (29.6 %) and in 12 patients (37.5 %) in group 2, the difference not being statistically significant (p = 0.52). Conclusions: Continuous thoracic paravertebral block for 48 hours is a good technique for the management of postoperative pain after pulmonary resection by thoracotomy. With moderate doses of local anesthetics (bupivacaine 0.20 %) we achieved good pain control and observed few systemic complications than major doses (bupivacaine 0.30 %) (AU)

Antecedentes y objetivos: El manejo del dolor post-toracotomía debe basarse en un enfoque multimodal que incluye la analgesia regional continua. El objetivo de este estudio fue comparar la eficacia analgésica de dos concentraciones de bupivacaína (0,2 y 0,3 %) a través de un catéter paravertebral, ambos grupos más fentanilo 2 mcg/ml. Material y métodos: Se realizó un ensayo clínico aleatorizado, doble ciego, para comparar estas dos concentraciones en pacientes sometidos a resección pulmonar por toracotomía en el Hospital Universitario Donostia entre noviembre de 2010 y mayo de 2011 (n = 59). El catéter paravertebral se colocó antes de la intervención quirúrgica, con el paciente despierto en posición sentada. Los datos se analizaron sobre la base de intención de tratar. Se utilizó la prueba de Chi cuadrado para variables cualitativas y la t de Student o pruebas de Mann-Whitney-Wilcoxon para las variables cuantitativas, en función de la distribución de las variables. El análisis estadístico se realizó utilizando el software de IBM SPSS (versión 17). Resultados: No se encontraron diferencias estadísticamente significativas en la función pulmonar postoperatoria (p = 0,49), la percepción subjetiva de dolor (VAS; p = 0,28) o el consumo Antecedentes y objetivos: El manejo del dolor post-toracotomía debe basarse en un enfoque multimodal que incluye la analgesia regional continua. El objetivo de este estudio fue comparar la eficacia analgésica de dos concentraciones de bupivacaína (0,2 y 0,3 %) a través de un catéter paravertebral, ambos grupos más fentanilo 2 mcg/ml. Material y métodos: Se realizó un ensayo clínico aleatorizado, doble ciego, para comparar estas dos concentraciones en pacientes sometidos a resección pulmonar por toracotomía en el Hospital Universitario Donostia entre noviembre de 2010 y mayo de 2011 (n = 59). El catéter paravertebral se colocó antes de la intervención quirúrgica, con el paciente despierto en posición sentada. Los datos se analizaron sobre la base de intención de tratar. Se utilizó la prueba de Chi cuadrado para variables cualitativas y la t de Student o pruebas de Mann-Whitney-Wilcoxon para las variables cuantitativas, en función de la distribución de las variables. El análisis estadístico se realizó utilizando el software de IBM SPSS (versión 17). Resultados: No se encontraron diferencias estadísticamente significativas en la función pulmonar postoperatoria (p = 0,49), la percepción subjetiva de dolor (VAS; p = 0,28) o el consumo de morfina acumulada (p = 0,101) en los dos grupos. Hemos observado efectos adversos en 8 pacientes del grupo 1 (29,6 %) y en 12 pacientes (37,5 %) del grupo 2; la diferencia no fue estadísticamente significativa (p = 0,52). Conclusiones: El bloqueo paravertebral torácico continuo durante 48 horas es una buena técnica para el manejo del dolor postoperatorio después de la resección pulmonar por toracotomía. Con dosis moderadas de anestésicos locales (bupivacaína 0,20 %) se logró un buen control del dolor y observamos un número menor de complicaciones sistémicas que el grupo de dosis mayores (bupivacaína 0,30 %) (AU)

Stability of pharmaceutical salts in solid oral dosage forms.

Using pharmaceutical salts in solid dosage forms can raise stability concerns, especially salt dissociation which can adversely affect the product performance. Therefore, a thorough understanding of the salt instability encountered in solid-state formulations is imperative to ensure the product quality. The present article uses the fundamental theory of acid base, ionic equilibrium, relationship of pH and solubility as a starting point to illustrate and interpret the salt formation and salt disproportionation in pharmaceutical systems. The criteria of selecting the optimal salt form and the underlying theory of salt formation and disproportionation are reviewed in detail. Factors influencing salt stability in solid dosage forms are scrutinized and discussed with the case studies. In addition, both commonly used and innovative strategies for preventing salt dissociations in formulation, on storage and during manufacturing will be suggested herein. This article will provide formulation scientists and manufacturing engineers an insight into the mechanisms of salt disproportionation and salt formation, which can help them to avoid and solve the instability issues of pharmaceutical salts in the product design.

Use of Bayesian Methods to Analyze and Visualize Content Uniformity Capability Versus United States Pharmacopeia and ASTM Standards.

The purpose of this work was to develop a straightforward and robust approach to analyze and summarize the ability of content uniformity data to meet different criteria. A robust Bayesian statistical analysis methodology is presented which provides a concise and easily interpretable visual summary of the content uniformity analysis results. The visualization displays individual batch analysis results and shows whether there is high confidence that different content uniformity criteria could be met a high percentage of the time in the future. The 3 tests assessed are as follows: (a) United States Pharmacopeia Uniformity of Dosage Units <905>, (b) a specific ASTM E2810 Sampling Plan 1 criterion to potentially be used for routine release testing, and (c) another specific ASTM E2810 Sampling Plan 2 criterion to potentially be used for process validation. The approach shown here could readily be used to create similar result summaries for other potential criteria.