AAPS PharmSciTech

Latuda® is an oral tablet approved by the US Food and Drug Administration (FDA) for the treatment of schizophrenia. However, the clinical efficacy of Latuda® is compromised by patient noncompliance due to frequent daily administration, especially for patients experiencing severe schizophrenia, whose medication is often needed for several months to years. Hence, developing a long-acting injectable formulation of lurasidone is urgently needed. Herein, a poorly water-soluble lurasidone pamoate (LP) salt was synthesized via the facile ion pair-based salt formation technology...

Glioma, in which a malignant tumor cell occurs in neural mesenchymal cells, has a rapid progression and poor prognosis, which is still far from desirable in clinical treatments. We developed a lab-on-a-chip (LOC) device for the rapid and efficient preparation of vitexin/indocyanine green (ICG) liposomes. Vitexin could be released from liposome to kill cancer cell, which can potentially improve the glioma therapeutic effect and reduce the treatment time through synergistic photodynamic/photothermal therapies (PDT/PTT)...

Biopharmaceuticals are large, complex and labile therapeutic molecules prone to instability due to various factors during manufacturing. To ensure their safety, quality and efficacy, a wide range of critical quality attributes (CQAs) such as product concentration, aggregation, particle size, purity and turbidity have to be met. Size exclusion chromatography (SEC) is the gold standard to measure protein aggregation and degradation. However, other techniques such as dynamic light scattering (DLS) are employed in tandem to measure the particle size distribution (PSD) and polydispersity of biopharmaceutical formulations...

A jet nebulizer sprays a fine mist or aerosol directly into the lungs to reduce inflammation, expand airways, and make breathing easier for respiratory patients. Asthma, COPD, emphysema, and cystic fibrosis are treated with jet nebulizers. They are chosen over other nebulizers for their shorter treatment time and wider medication compatibility. For mechanically ventilated patients, jet nebulizers humidify oxygen to provide bronchodilators, antibiotics, and other respiratory medications. Additionally, they treat pneumonia, bronchitis, and other lung infections...

Methods for estimating pharmaceutical shelf life based on tolerance intervals are proposed by Schwenke, et al. AAPS PharmSciTech. 2020;21:290, [1] where a critical quality attribute that follows a simple linear (straight line) response trend across storage time is presented as the traditional example. A random coefficient mixed linear regression model is used to characterize the between batch and within batch variation. These methods are further discussed for various stability study scenarios, number of stability batches, and levels of assumed risk in Schwenke, et al...

No abstract text is available yet for this article.

Amorphous and crystalline active pharmaceutical ingredients (APIs) are both widely studied for pulmonary delivery. The past research mainly studied the impact of solid-state properties on pharmacokinetic attributes; however, the influence of solid-state properties on aerosolization performance was much less studied. This study aimed to investigate the different aerosolization performances of amorphous and crystalline curcumin (Cur) stabilized with L-leucine. Cur was spray-dried with different concentrations of L-leucine (0, 5, 20, 35, and 50%, w/w) as both solution-based and suspension-based formulations to acquire amorphous and crystalline Cur powders...

All-trans retinoic acid and arsenic trioxide are the leading choices for the treatment of acute promyelocytic leukemia. Notwithstanding the impressive differentiative properties of all-trans retinoic acid and the apoptotic properties of arsenic trioxide, some problems still occur in acute promyelocytic leukemia treatment. These problems are due to patients' relapses, mainly related to changes in the ligand-binding domain of RARα (retinoic acid receptor α) and the cardiotoxic effects caused by arsenic trioxide...

No abstract text is available yet for this article.

Infectious diseases are still the major issue not only due to antibiotic resistance but also causing deaths if not diagnosed at early-stages. Different approaches including nanosized drug delivery systems and theranostics are researched to overcome antibiotic resistance, decrease the side effects of antibiotics, improve the treatment response, and early diagnose. Therefore, in the present study, nanosized, radiolabeled with 99m Tc, colistin encapsulated, neutral and cationic liposome formulations were prepared as the theranostic agent for Pseudomonas aeruginosa infections...

Pharmaceutical industries and drug regulatory agencies are inclining towards continuous manufacturing due to better control over the processing conditions and in view to improve product quality. In the present work, continuous manufacturing of O/W emulgel by melt extrusion process was explored using lidocaine as an active pharmaceutical ingredient. Emulgel was characterized for pH, water activity, globule size distribution, and in vitro release rate. Additionally, effect of temperature (25°C and 60°C) and screw speed (100, 300, and 600 rpm) on the globule size and in vitro release rate was studied...

The main development process of periodontitis involves periodontal pathogenic bacteria as the initiating factor causing the onset of destructive inflammation, which in turn stimulates the destruction of periodontal tissue. It is difficult to achieve the eradication of periodontitis due to the complex interaction among antibacterial, anti-inflammatory, and bone restoration. Herein, we propose an antibacterial-anti-inflammatory-bone restoration procedural treatment strategy with minocycline (MIN) for the efficient treatment of periodontitis...

Multiple sources must be consulted to determine the most appropriate procedures for the laboratory-based performance evaluation of aqueous oral inhaled products (OIPs) for the primary measures, dose uniformity/delivery, and aerodynamic particle (droplet) size distribution (APSD). These sources have been developed at different times, mainly in Europe and North America, during the past 25 years by diverse organizations, including pharmacopeial chapter/monograph development committees, regulatory agencies, and national and international standards bodies...

The present study was aimed to the development and characterization of valsartan-containing buccal films with an introduction to a novel technique of image analysis. Visual inspection of the film provided a wealth of information that was difficult to quantify objectively. The obtained images of the films observed under the microscope were embedded in a convolutional neural network (CNN). The results were clustered according to their visual quality and on the basis of data distances. Image analysis proved to be a promising method to characterize buccal films appearance and their visual properties...

Lewisite is a highly toxic chemical warfare agent that leads to cutaneous and systemic damage. N-acetylcysteine (NAC) and 4-phenylbutryic acid (4-PBA) are two novel antidotes developed to treat toxicity caused by lewisite and similar arsenicals. Our in vivo studies demonstrated safety and effectiveness of these agents against skin injury caused by surrogate lewisite (Phenylarsine oxide) proving their potential for the treatment of lewisite injury. We further focused on exploring various enhancement strategies for an enhanced delivery of these agents via skin...

The continuous manufacturing (CM) of solid oral dosage forms has received increased attention in recent years and has become a leading technology in the pharmaceutical industry. A model has been developed based on process data from two design of experiments (DoEs), where the impact of the mixer process parameters, throughput (THR), hold up mass (HUM), impeller speed (IMP), and the input raw material bulk density (BDi ), on the continuous process and the resulting drug product has been investigated. These statistical models revealed equations, describing process parameter interactions for optimization purposes...

In order to better promote the application of the polymeric mixed micelles (PMMs) in oral delivery, in addition to focusing on the improvement of micellar structural stability, it is necessary to obtain the absorption characteristics of the intact micellar particles. In this work, the transport behavior across Caco-2 cells of FS/PMMs composed of Pluronic F127 and Solutol HS15 was tracked by encapsulating an environment-responsive probe into the particles. The specific property of the probe is the water-initiated aggregation-caused quenching (ACQ) ability, by which integral particles can be identified accurately...

The aim of this study was the improvement of rutin solubility along with targeting its release to colon for effective treatment of colon cancer. Five formulations of compression-coated tablets were prepared with the same core composition including rutin-polyvinyl pyrrolidone K30 solid dispersion (rutin-PVP K30 SD) but differ in being coated with either frankincense alone or different combinations of frankincense with gelatin. The superior formula was selected based on the in vitro drug release then further evaluated in terms of physical properties and in vivo performance in dogs using X-ray...

It is well-known that plenty of active pharmaceutical ingredients (API) inherently possess an unpleasant taste, which influences the acceptance of patients, especially children. Therefore, manufacturing taste-masked dosage forms has attracted a lot of attention. This review describes in detail the taste-masking technologies based on the difference in the taste transmission mechanism which is currently available. In particular, the review highlights the application of various methods, with a special focus on how to screen the appropriate masking technology according to the properties of API...

The physiologically relevant dissolution apparatuses simulate various aspects of gastrointestinal physiology and help to understand and predict the in vivo behavior of an oral dosage form. In this paper, we present and characterize for the first time a novel bio-relevant dissolution apparatus - PhysioCell®; . We evaluated the impact of several factors on the hydrodynamic conditions in the key vessel of the apparatus - the StressCell. We observed that the medium flow rate, but not the glass beads' size or amount, significantly influenced the dissolution rate...