The Selection of a Pharmaceutical Salt—The Effect of the Acidity of the Counterion on Its Solubility and Potential Biopharmaceutical Performance

A roadmap for the selection of a pharmaceutical salt form for a development candidate is presented. The free base of the candidate did not have sufficient chemical stability for development. The initially selected salt form turned out to be undevelopable because it was unstable during scale-up synthesis and storage. The rationale for the new solid form screening and the criteria for selection are discussed. Before the final selection, the pH solubility profiles of the 2 new salts, a benzoate and a besylate, were compared. Atypical solubility behavior was observed for the benzoate salt in hydrochloric acid with and without normal saline. A scheme is proposed illustrating how the pKas of the counterion and active pharmaceutical ingredient, the medium composition, and final pH affect the solubility and solution equilibria of the 2 selected salt forms. This scheme also includes the equilibria between solution and solid phases in different pH ranges. The pharmaceutical importance of this research is that it sheds light on how the acidity of the counterion can affect the solubility of the selected salt form in the gastric environment. With a well-designed formulation strategy, this property potentially can be translated to optimal biopharmaceutical performance of the drug product.     

Cytokine-targeted therapy for the management of solid organ transplant recipients

IntroductionThe number of solid organ transplants completed annually continues to trend upwards each year. Despite this, maintenance immunosuppression available on the market has remained relatively stagnant. Standard triple immunosuppression, composed typically of tacrolimus, mycophenolate, and steroids, lead to many side effects that limit the use of these medications. Tacrolimus, specifically, causes nephrotoxicity that can lead to renal dysfunction requiring a kidney transplant down the road. Alternative therapies for the management of immunosuppression need to be identified to try to mitigate these adverse effects.BodyCytokines are responsible for facilitating T cell differentiation and lead to the activation of inflammatory mediators that can contribute to graft damage and ultimately rejection. IL-4, IL-6, IL-12/23, and IL-15 are attractive targets for medications to try to ameliorate graft rejection. Various cytokine-targeted medications are currently available on the market for the treatment of inflammatory and autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, Crohn’s, and multiple sclerosis.ConclusionThis article reviews cytokine involvement in alloimmunity and the potential role cytokine-targeted therapy may play in prevention of allograft rejection in solid organ transplant recipients.     

Metabolic syndrome: pathogenesis, medical care and dental implications

BACKGROUND: The dental literature contains little information about metabolic syndrome (MetS) and its dental implications. TYPES OF STUDIES REVIEWED: The authors conducted a MEDLINE search for the period 2000 through 2005, using the term "metabolic syndrome" to define its pathophysiology, medical treatment and dental implications. RESULTS: MetS is the co-occurrence of abdominal obesity, hyper-triglyceridemia, reduced high-density lipoprotein cholesterol levels, hypertension and impaired fasting glucose, which results from consumption of a high-calorie diet and decreased levels of physical activity superimposed on the appropriate genetic setting. Components of MetS synergistically promote the development of atherosclerosis, resulting in myocardial infarction and stroke. CLINICAL IMPLICATIONS: Deteriorating oral health status is associated with worsening of the atherogenic profile. Tooth loss often results in chewing difficulties because of inadequate occlusive surfaces and may lead to alterations in food selection and dietary quality. This, in turn, adversely affects body composition and nutritional status, both of which are related to vascular health. Dentists should develop treatment plans that preserve and restore the dentition, thus ensuring maximum masticatory efficiency and affording patients the optimum opportunity to consume food that will not foster atherogenesis.     

Feasibility of a Kinect®-based rehabilitation strategy after burn injury

Introduction

The advent of consoles that deliver both interactive games and therapy may augment rehabilitation options in burn patients. The Jintronix software combines therapy-specific software and interactive gaming as a form of coaching and records patient performance on the Kinect^® platform. Our objective was to determine the feasibility of a set of Jintronix games and therapy modules in hospitalized adult burn patients.

Protein tyrosine phosphatase conjugated with a novel transdermal delivery peptide,astrotactin 1–derived peptide recombinant protein tyrosine phosphatase (AP-rPTP), alleviates both atopic dermatitis–like and psoriasis-like dermatitis

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Mechanisms and biomarkers of immune quiescence in kidney transplantation

This review discusses the current understanding of biomarkers of immune quiescence based on reviews of published literature in kidney transplant operational tolerance and mechanistic studies based on a better characterization of the stable, well-functioning renal allograft.     

Analysis of the adverse reactions of atezolizumab: A real-world study based on FAERS database

Objective In this study, we aimed to determine the incidence of adverse drug reactions (ADRs) of atezolizumab, identify ADR signals that are significantly related to atezolizumab, and provide a reference for the rational use of atezolizumab in the clinic through the statistical analysis of its adverse drug events (ADEs) reported in the American Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database. Methods In total, 4796 cases of atezolizumab ADEs reported in the American FAERS database from 2017 to 2019 were retrospectively analyzed. Results The top three ADEs were febrile neutropenia (3.7％), anemia (2.9％), and acute renal failure (2.3％). In addition, the incidence rates of some ADEs were significantly different according to sex and age. The systematic organ classification of atezolizumab ADEs involved 32 systems, among which the top three were blood and lymphatic system disorders (585 cases, 12.2％), gastrointestinal disorders (433 cases, 9.0％), and infections and infestations (401 cases, 8.4％). The reporting odds ratio (ROR) method was used to detect the ADR signals of atezolizumab. The ROR (95％ confidence interval) of the top ADE, febrile neutropenia, was 39.236 (33.757–45.604). In addition, we found 121 cases of complications associated with immune-related ADEs. Conclusion The ADRs of atezolizumab reported in the FAERS database were consistent with those mentioned in the instructions for atezolizumab use, suggesting that atezolizumab has an acceptable and controllable drug effect.