Sugars and Polyols of Natural Origin as Carriers for Solubility and Dissolution Enhancement.

Crystalline carriers such as dextrose, sucrose, galactose, mannitol, sorbitol, and isomalt have been reported to increase the solubility, and dissolution rates of poorly soluble drugs when employed as carriers in solid dispersions (SDs). However, synthetic polymers dominate the preparation of drugs: excipient SDs have been created in recent years, but these polymer-based SDs exhibit the major drawback of recrystallisation upon storage. Also, the use of high-molecular-weight polymers with increased chain lengths brings forth problems such as increased viscosity and unnecessary bulkiness in the resulting dosage form. An ideal SD carrier should be hydrophilic, non-hygroscopic, have high hydrogen-bonding propensity, have a high glass transition temperature (Tg), and be safe to use. This review discusses sugars and polyols as suitable carriers for SDs, as they possess several ideal characteristics. Recently, the use of low-molecular-weight excipients has gained much interest in developing SDs. However, there are limited options available for safe, low molecular excipients, which opens the door again for sugars and polyols. The major points of this review focus on the successes and failures of employing sugars and polyols in the preparation of SDs in the past, recent advances, and potential future applications for the solubility enhancement of poorly water-soluble drugs.

A Comprehensive Review of Cross-Linked Gels as Vehicles for Drug Delivery to Treat Central Nervous System Disorders.

Gels are attractive candidates for drug delivery because they are easily producible while offering sustained and/or controlled drug release through various mechanisms by releasing the therapeutic agent at the site of action or absorption. Gels can be classified based on various characteristics including the nature of solvents used during preparation and the method of cross-linking. The development of novel gel systems for local or systemic drug delivery in a sustained, controlled, and targetable manner has been at the epitome of recent advances in drug delivery systems. Cross-linked gels can be modified by altering their polymer composition and content for pharmaceutical and biomedical applications. These modifications have resulted in the development of stimuli-responsive and functionalized dosage forms that offer many advantages for effective dosing of drugs for Central Nervous System (CNS) conditions. In this review, the literature concerning recent advances in cross-linked gels for drug delivery to the CNS are explored. Injectable and non-injectable formulations intended for the treatment of diseases of the CNS together with the impact of recent advances in cross-linked gels on studies involving CNS drug delivery are discussed.

The Validation of a Simple, Robust, Stability-Indicating RP-HPLC Method for the Simultaneous Detection of Lamivudine, Tenofovir Disoproxil Fumarate, and Dolutegravir Sodium in Bulk Material and Pharmaceutical Formulations.

An effective analytical method is requisite to ensure the accurate identification and quantification of drug(s), either in bulk material or in complex matrices, which form part of finished pharmaceutical products. For the purpose of a pharmaceutical formulation study, it became necessary to have a simple, yet robust and reproducible reversed-phase HPLC method for the simultaneous detection and quantification of lamivudine (3TC), tenofovir disoproxil fumarate (TDF), and dolutegravir sodium (DTG) in bulk form, complex polymeric matrices, and during drug release studies. A suitable method was developed using a Kinetex® C18, 250 × 4.6 mm column as stationary phase and a mobile phase consisting of 50 : 50 v/v methanol and water with 1 mL orthophosphoric acid, with a flow rate of 1.0 mL/min and column temperature maintained at 35°C. A detection wavelength of 260 nm and an injection volume of 10 µL were used. The method was validated according to the International Conference on Harmonization (ICH) guideline Q2 (R1), and the parameters of linearity and range, accuracy, precision, specificity, limit of detection (LOD), limit of quantification (LOQ), robustness, and stability were all determined. Acceptable correlation coefficients for linearity (R2) of >0.998 for each of the three drugs were obtained. The LOD was quantified to be 56.31 µg/mL, 40.27 µg/mL, and 7.00 µg/mL for 3TC, TDF, and DTG, respectively, and the LOQ was quantified as 187.69 µg/mL, 134.22 µg/mL, and 22.5 µg/mL for 3TC, TDF, and DTG, respectively. In relation to all the determined validation parameters, this method proves to be suitable for the accurate identification and quantification of the three ARVs, either alone or in combination, as well as when incorporated into polymeric matrices. Furthermore, the method proves to be suitable to detect degradation of the compounds.

COVID-19: Guidelines for pharmacists in South Africa.

Since the outbreak of COVID-19, and its declaration as a pandemic by the World Health Organization (WHO), the reliance on pharmacists as one of the first points of contact within the healthcare system has been highlighted. This evidence-based review is aimed at providing guidance for pharmacists in community, hospital and other settings in South Africa, on the management of patients with suspected or confirmed coronavirus disease 2019, or COVID-19. The situation is rapidly evolving, and new evidence continues to emerge on a daily basis. This guidance document takes into account and includes newly available evidence and recommendations, particularly around the following aspects relating to COVID-19: EpidemiologyThe virus, its modes of transmission and incubation periodSymptom identification, including the differentiation between influenza, allergic rhinitis, sinusitis and COVID-19Social media myths and misinformationTreatment guidelines and medicines that may need to be kept in stockTreatment and prevention options, including an update on vaccine developmentThe case for and against the use of NSAIDs, ACE-inhibitors and angiotensin receptor blockers (ARBs) in patients with COVID-19Interventions and patient counselling by the pharmacist. It is critical, though, that pharmacists access the most recent and authoritative information to guide their practice. Key websites that can be relied upon are: World Health Organization (WHO): https://www.who.int/emergencies/diseases/novel-coronavirus-2019National Institute for Communicable Diseases (NICD): https://www.nicd.ac.za/diseases-a-z-index/covid-19/National Department of Health (NDoH): http://www.health.gov.za/index.php/outbreaks/145-corona-virus-outbreak/465-corona-virus-outbreak; https://sacoronavirus.co.za/.

COVID-19: Guidelines for pharmacists in South Africa

Since the outbreak of COVID-19, and its declaration as a pandemic by the World Health Organization (WHO), the reliance on pharmacists as one of the first points of contact within the healthcare system has been highlighted. This evidence-based review is aimed at providing guidance for pharmacists in community, hospital and other settings in South Africa, on the management of patients with suspected or confirmed coronavirus disease 2019, or COVID-19. The situation is rapidly evolving, and new evidence continues to emerge on a daily basis. This guidance document takes into account and includes newly available evidence and recommendations, particularly around the following aspects relating to COVID-19: • Epidemiology • The virus, its modes of transmission and incubation period • Symptom identification, including the differentiation between influenza, allergic rhinitis, sinusitis and COVID-19 • Social media myths and misinformation • Treatment guidelines and medicines that may need to be kept in stock • Treatment and prevention options, including an update on vaccine development • The case for and against the use of NSAIDs, ACE-inhibitors and angiotensin receptor blockers (ARBs) in patients with COVID-19 • Interventions and patient counselling by the pharmacist. It is critical, though, that pharmacists access the most recent and authoritative information to guide their practice. Key websites that can be relied upon are: • World Health Organization (WHO): https://www.who.int/emergencies/diseases/novelcoronavirus-2019 • National Institute for Communicable Diseases (NICD): https://www.nicd.ac.za/diseasesa-z-index/covid-19/ • National Department of Health (NDoH): http://www.health.gov.za/index.php/ outbreaks/145-corona-virus-outbreak/465-corona-virus-outbreak; https://sacoronavirus. co.za/

The physical stability of drugs linked to quality-by-design (QbD) and in-process technology (PAT) perspectives.

The physical stability of solid-state forms in which drugs may exist is in some sense an overlooked aspect. In an era where strategies such as amorphous solid dispersions or co-amorphous preparations might provide answers to stumbling blocks such as poor drug solubility and bioavailability, the physical stability of such solid-state preparations should be a priority. Furthermore, the pharmaceutical industry is moving towards adapting a real time release of pharmaceutical products strategy, through the utilization of process analytical technology. It is thus becoming imperative to investigate the various types of phase transformations a specific solid-state form of a drug may undergo. Also, to critically assess the applicability of process analytical tools that may be sensitive enough to monitor not only chemical but also physical drug stability. These combined efforts allow quality to be built into the product, rather than dealing with costly post batch release recalls. Given that drug stability is an essential quality attribute for a drug product and the quality-by-design approach (QbD) is a best solution to build quality in all pharmaceutical products we focussed on the critical material attributes (CMAs), specifically relating to the physical stability of any given drug. This review highlights physical drug stability in relation to CMAs and how this ultimately link to the finished pharmaceutical product. Investigated challenges associated current PAT strategies is also discussed.

Different amorphous solid-state forms of roxithromycin: A thermodynamic and morphological study.

The striking impact that different preparation methods have on the characteristics of amorphous solid-state forms has attracted considerable attention during the last two decades. The pursuit of more extensive knowledge regarding polyamorphism therefore continues. The aim of this study was firstly, to investigate the influence of different preparation techniques to obtain amorphous solid-state forms for the same active pharmaceutical ingredient, namely roxithromycin. The preparation techniques also report on a method utilizing hot air, which although it is based on a melt intermediary step, is considered a novel preparation method. Secondly, to conduct an in-depth investigation into any physico-chemical differences between the resulting amorphous forms and thirdly, to bring our findings into context with that of previous work done, whilst simultaneously discussing a well-defined interpretation for the term polyamorphism and propose a discernment between true polyamorphism and pseudo-polyamorphism/atypical-polyamorphism. The preparation techniques included melt, solution, and a combination of solution-mechanical disruption as intermediary steps. The resulting amorphous forms were investigated using differential scanning calorimetry, X-ray powder diffraction, hot-stage microscopy, scanning electron microscopy, and vapor sorption. Clear and significant thermodynamic differences were determined between the four amorphous forms. It was also deduced from this study that different preparation techniques have a mentionable impact on the morphological properties of the resulting amorphous roxithromycin powders. Thermodynamic properties as well as the physical characteristics of the amorphous forms greatly governed other physico-chemical properties i.e. solubility and dissolution.

Amorphous Sulfadoxine: A Physical Stability and Crystallization Kinetics Study.

Poor aqueous solubility of drugs and the improvement thereof has always been a challenge for the pharmaceutical industry. With this, one of the focuses of the pharmaceutical research scientist involves investigating possible metastable forms of a given drug to be incorporated into solid dosage forms. The rationale being, the improved solubility offered by the metastable solid-state forms of drugs. Solubility remains a major challenge for formulation scientists, especially with antimicrobial agents where the emergence of resistance is directly dependent on the concentration and duration of the parasite exposed to the drug. Sulfadoxine-pyrimethamine combination therapies are still the recommended treatments for uncomplicated Plasmodium falciparum malaria. The aim of this study was to prepare an amorphous form of sulfadoxine and to investigate the stability and recrystallization behavior thereof. The amorphous form was prepared by the well-known quench cooling of the melt. The physico-chemical properties and stability of amorphous sulfadoxine were studied using hot-stage microscopy (HSM), scanning electron microscopy (SEM), x-ray powder diffractometry (XRPD), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), as well as microcalorimetry. The recrystallization kinetics were studied isothermally by applying the Johnson-Mehl-Avrami model and non-isothermally by applying the Kissinger model. The physical stabilization of the amorphous form was investigated using physical mixtures of amorphous sulfadoxine with polyvinylpyrrolidone-25 (PVP-25). It was proved that sulfadoxine is a good glass former with relative high physical stability; however, water acts as a strong plasticizer for amorphous sulfadoxine, detrimentally affecting the stability during exposure to high moisture conditions.

The Stabilization of Amorphous Zopiclone in an Amorphous Solid Dispersion.

Zopiclone is a poorly soluble psychotherapeutic agent. The aim of this study was to prepare and characterize an amorphous form of zopiclone as well as the characterization and performance of a stable amorphous solid dispersion. The amorphous form was prepared by the well-known method of quench-cooling of the melt. The solid dispersion was prepared by a solvent evaporation method of zopiclone, polyvinylpyrrolidone-25 (PVP-25), and methanol, followed by freeze-drying. The physico-chemical properties and stability of amorphous zopiclone and the solid dispersion was studied using differential scanning calorimetry (DSC), infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), hot-stage microscopy (HSM), X-ray diffractometry (XRD), solubility, and dissolution studies. The zopiclone amorphous solid-state form was determined to be a fragile glass; it was concluded that the stability of the amorphous form is influenced by both temperature and water. Exposure of amorphous zopiclone to moisture results in rapid transformation of the amorphous form to the crystalline dihydrated form. In comparison, the amorphous solid dispersion proved to be more stable with increased aqueous solubility.