Modulation of the powder properties of lamotrigine by crystal forms

The mechanical properties of powders determine the ease of manufacture and ultimately the quality of the oral solid dosage forms. Although poor mechanical properties of an active pharmaceutical ingredient (API) can be mitigated by using suitable excipients in a formulation, the effectiveness of that approach is limited for high dose drugs or multidrug tablets. In this context, improving the mechanical properties of the APIs through solid form optimisation is a good strategy to address such a challenge. This work explores the powder and tableting properties of various lamotrigine (LAM) solid forms with the aim to facilitate direct compression by overcoming the poor tablet ability of LAM. The two drug-drug crystals of LAM with nicotinamide and valproic acid demonstrate superior flowability and tablet ability over LAM. The improved powder properties are rationalised by structure analysis using energy framework, scanning electron microscopy, and Heckel analysis

Pharmaceutical cocrystals: from serendipity to design to application

The field of pharmaceutical cocrystals has reached a tipping point, particularly because cocrystals can improve the physicochemical properties of drugs without compromising their therapeutic benefit. Accounts of cocrystal investigations in the literature started in earnest in 2003 and patent applications soon followed. The frequency of both has steadily accelerated, demonstrating an enhanced understanding of the design, characterisation, and manufacture of cocrystals and heightened interest from industry. Indeed, there were four new product approvals from 2014 to 2017 and more are in the pipeline. Here, we review all marketed drug products that are based upon pharmaceutical cocrystal drug substances, starting with the first recorded example, Beta-Chlor® in 1963, with a particular emphasis on their discovery, rationale for use, and market impact

Formulating a stable mannitol infusion while maintaining hyperosmolarity

Mannitol infusion is commonly used in the treatment of intracranial hypertension following traumatic brain injury. It has long been known to have stability issues, specifically, mannitol recrystallises from solutions greater than 10% w/v in ambient conditions. This can happen at any time, whether on the pharmacy shelf or during a medical procedure. This study describes the stability limits of 20% w/v mannitol infusion (the most common strength used clinically) and proposes a number of safer, stable and tuneable hyperosmotic formulations of mannitol in combination with clinically acceptable osmotic agents (NaCl, sorbitol and glycerol)

More than coffee – a World Café to explore enablers of pharmacy practice research

.Background Pharmacists are in demand now more than ever to provide high‐quality expertise about the effectiveness, safety and use of medications. Amidst an increasingly complex and costly healthcare system, policy makers need robust evidence to justify public spending on pharmacy services. Research on the impact of existing and emerging pharmacy practices is required. Objective To explore barriers and opportunities to enhance research among pharmacists in Ireland utilising a World Café methodology. Methods A pharmacy research discussion day was held in November 2018, open to all pharmacists in Ireland. A World Café methodology was utilised as a mechanism to facilitate group discussions about pharmacy practice research. Results Discussions with 63 attendees identified four themes and seventeen subthemes. The four themes were challenges undertaking research, research motivations, leadership and training. Subthemes included robust evidence, clinical, economic and societal outcomes, alignment with national and international health system priorities, need for incentives from professional training bodies, competitive business model and embed within schools of pharmacy. Conclusions The most commonly discussed barriers inhibiting research were workload, technology limitations and financial considerations. Organisational leadership to prioritise and coordinate research efforts, training to build research capacity, building on existing examples of excellence and initiation of bottom‐up community‐based research projects were identified in our study as opportunities to enhance pharmacist involvement in research and ultimately patient health outcomes

Investigating structural property relationships to enable repurposing of pharmaceuticals as zinc ionophores

The importance of zinc in biology has gained greater recognition in recent years due to its essential contributions to the function of many endogenous enzymes. Disruption of zinc homeostasis may be useful in treating pathological conditions, such as Alzheimer’s, and for antiviral purposes. Despite the growth of knowledge and increased interest in zinc, little is known about the structure and function of zinc ionophores. In this study we analyse the Cambridge Structural Database and solution complexation studies found in the literature to identify key functional groups which may confer zinc ionophorism. Pharmaceuticals, nutraceuticals and amino acids with these functionalities were selected to enable us to explore the translatability of ionophoric activity from in vitro assays to cellular systems. We find that although certain species may complex to zinc in the solid and solution states, and may carry ions across simple membrane systems, this does not necessarily translate into ionophoric activity. We propose that the CSD can help refine key functionalities but that ionophoric activity must be confirmed in cellular systems

Highly selective trace ammonium removal from dairy wastewater streams by aluminosilicate materials

Water is a key solvent, fundamental to supporting life on earth. It is equally important in many industrial processes, particularly within agricultural and pharmaceutical industries, which are major drivers of the global economy. The results of water contamination by common activity in these industries is well known and EU Water Quality Directives and Associated Regulations mandate that NH4+ concentrations in effluent streams should not exceed 0.3 mg L−1, this has put immense pressure on organisations and individuals operating in these industries. As the environmental and financial costs associated with water purification begin to mount, there is a great need for novel processes and materials (particularly renewable) to transform the industry. Current solutions have evolved from combating toxic sludge to the use of membrane technology, but it is well known that the production of these membrane technologies creates a large environmental footprint. Zeolites could provide an answer; their pore size and chemistry enable efficient removal of aqueous based cations via simple ion exchange processes. Herein, we demonstrate efficient removal of NH4+ via both static and dynamic methodology for industrial application. Molecular modelling was used to determine the cation–framework interactions which will enable customisation and design of superior sorbents for NH4+ capture in wastewater

Tuning the pharmacokinetic performance of quercetin by cocrystallization

Quercetin (QUE) is a widely studied nutraceutical with a number of potential therapeutic properties. Although QUE is abundant in the plant kingdom, its poor solubility (≤20 μg/mL) and poor oral bioavailability have impeded its potential utility and clinical development. In this context, cocrystallization has emerged as a useful method for improving the physicochemical properties of biologically active molecules. We herein report a novel cocrystal of the nutraceutical quercetin (QUE) with the coformer pentoxifylline (PTF) and a solvate of a previously reported structure between QUE and betaine (BET). We also report the outcomes of in vitro and in vivo studies of QUE release and absorption from a panel of QUE cocrystals: betaine (BET), theophylline (THP), l-proline (PRO), and novel QUEPTF. All cocrystals were found to exhibit an improvement in the dissolution rate of QUE. Further, the QUE plasma levels in Sprague–Dawley rats showed a 64-, 27-, 10- and 7-fold increase in oral bioavailability for QUEBET·MeOH, QUEPTF, QUEPRO, and QUETHP, respectively, compared to QUE anhydrate. We rationalize our in vivo and in vitro findings as the result of dissolution–supersaturation–precipitation behavior.</p