Oral solid dosage forms, the most widely used pharmaceutical products, are typically manufactured through a series of processes that transform a blend of drug and excipient particles into a densified ...product with consistent quality attributes. While the densification of powder during processing is crucial and directly impacts the quality of the drug product, there is still scarcity of non-destructive and fast sensor systems that provide access to the powder density at critical process stages. This review discusses methods for monitoring density variations of particulate matter by describing their principles and presenting application examples. The techniques discussed range from common in-line methods such as near-infrared spectroscopy, acoustic emission and ultrasonic methods as well as techniques with potential to be more frequently applied in a pharmaceutical manufacturing line, i.e., terahertz spectroscopy and imaging, microwave technique, electrical tomography and X-ray based methods. This review also compares these techniques in terms of measurement and data processing time, resolution and its ability to be integrated in a process.
Display omitted
•Review of sensors for powder density variation measurements during processing.•Focus on major conventional pharmaceutical solid oral dosage form processing routes.•Discussion on impact of variation in powder density on final product quality.•Principles, instrumentation and applications of common/emerging technologies.•Technology comparison: Data acquisition/processing, resolution, system integration.
Lumbar Disc Herniation (LDH) is a common condition, and contemporary pain research emphasizes the importance of adopting a comprehensive biopsychosocial perspective in pain treatment for positive ...clinical outcomes. Integrated Naturopathy and Yoga (INY) is a non-invasive medical system that takes a holistic and patient-centric approach to healing diseases. However, there is limited evidence on the effectiveness of INY, particularly in managing Sequestered LDH. We present two cases of patients experiencing radicular low back pain, lower limb weakness, and neuro-claudication who opted for conservative naturopathic management with INY. Following the INY treatments, both patients reported gradual relief from lower back pain, radicular pain, and neurological deficits. These findings are significant and contribute valuable evidence, suggesting that INY could be a viable therapeutic approach for managing sequestered LDH. This represents the first report on a non-invasive method for resolving sequestered LDH by utilizing INY.
Display omitted
Environmental conditions can have a profound impact on the bulk behaviour of pharmaceutical powders, including their tribo–charging tendency. Typically, high relative humidity (RH) ...has been associated to a reduction in the electrostatic charge of the material. However, the occurrence of charge mitigation seems to be related to the quantity of water molecules at the powder surface, which depends on intrinsic material attributes (i.e., water sorption propensity), and external factors (i.e., RH level). In the present study, pharmaceutical powders (i.e., microcrystalline cellulose, D–mannitol, paracetamol and magnesium stearate) were conditioned at three levels of RH, relevant for pharmaceutical operations, and their bulk behaviour, including charging propensity, was analyzed. Depending on the material type, powders sorbed water from the humid atmosphere to different extents, resulting in different charging behaviours. Overall, the charge density of the materials was found to decrease after a certain RH or monotonically decrease with an increase of RH, except for D–mannitol. For this material, a contrasting trend of increase in charging was observed with an increase in RH. Moreover, the powders showed a distinct tribo–charging sensitivity to RH, with paracetamol being the most affected. These findings suggest that a careful consideration on solid material–moisture interactions is needed when using RH as strategy to minimize electrostatic effects in powder processing.
The recent global pandemic of novel coronavirus disease 2019 (COVID-19) is increasingly alarming. As of 21 June 2020, there are more than 8.7 million cases worldwide, with 460 000 deaths. Nepal is ...not an exception to COVID-19 and is currently facing a challenge to prevent the spread of infection. The analysis of the detected cases, severity and outcomes of the cases within a country is important to have a clear picture of where the pandemic is heading and what measures should be taken to curb the infection before it becomes uncontrollable. We collected data regarding all the cases, recoveries and deaths attributed to COVID-19 in Nepal starting from the first case on 23 January to 21 June 2020. At present, COVID-19 has spread all over Nepal, with a rapid increase in the number of new cases and deaths, which is alarming in a low-income country with an inadequate healthcare system like Nepal. Although the government implemented early school closure and lockdown, the management to contain COVID-19 does not appear to be adequate. Understanding the current situation regarding COVID-19 in Nepal is important for providing a direction towards proper management of the disease.
Purpose
The performance of carrier-based dry powder inhaler (DPI) formulations can be critically impacted by interfacial interactions driven by tribo-electrification. Therefore, the aim of the ...present work was to understand how distinct API particle characteristics affect the charging behaviour of blends intended for DPI delivery.
Methods
Salbutamol sulphate (SBS) particles engineered via spray-drying and jet milling were used as model APIs. D-mannitol was selected as a model carrier. The materials were characterized concerning their different particle properties and their charge was analysed alone and in blends before and after flow over a stainless-steel pipe.
Results
The spray-dried SBS (amorphous and spherical) charged positively and to a higher extent than jet milled SBS (crystalline and acicular) that charged negatively and to a lower extent. D-mannitol charged positively and to a higher extent than the APIs. All drug-excipient blends charged negatively and differences were found between the spray-dried and jet milled SBS blends at 2% and 5% drug loads.
Conclusions
It was demonstrated how distinct solid-states, particle shape, size and morphology as well as different water contents of the different materials can affect tribo-charging. For their binary blends, the amount and nature of fines seem to govern inter-particle contacts critically impacting charge evolution.
Display omitted
The application of ethylene-vinyl acetate (EVA) copolymers in reservoir-type intra-vaginal rings (IVRs) offers advantages over silicones including i) versatile properties, ii) absence ...of curing chemistry, and iii) continuous and flexible processing via co-extrusion. Thus, we investigated the capability of EVA based IVRs to deliver broad ranges of estradiol (E2) thereby, fulfilling the requirements of local and systemic hormone replacement therapy (HRT) and contraception. To circumvent the high material needs associated with co-extrusion, we implemented a small-scale screening procedure that accurately predicts the E2 release from IVRs comprising E2 below its solubility concentration in the core. Rational formulation design yielded the target release for local HRT (<10 µg/day), systemic HRT (50–100 µg/day) and contraception (>150 µg/day, combined with a progestin). Low E2 release was achieved by the combination of low E2 loadings, low VA content of the membrane polymer (also known as coat polymer or outer shell), and increased membrane thickness. Medium E2 release was provided by medium E2 loading, low VA content of the membrane polymer, and low membrane thickness. Combining high E2 loadings, high VA content of the membrane polymer, and low membrane thickness yielded high E2 release. This makes EVA based IVRs a versatile platform that can be used to deliver a broad range of E2 doses.
Display omitted
Powder feeding is a crucial unit operation in continuous manufacturing (CM) of pharmaceutical products. Twin-screw feeders are typically employed to ensure the accurate mass flow of ...pharmaceutical materials throughout the production process. Here, contact and separation of particles can give rise to electrostatic charges, affecting feeder performance and final product quality. The knowledge of the material charging tendency would therefore be beneficial for both formulation and process design. At the early stage of product development, only a limited amount of material is available and the propensity of the powders to charge needs to be assessed on lab test equipment, which not necessarily represent the material state during processing. In this study, the tribo-charging behaviour of a set of common pharmaceutical materials (i.e., microcrystalline cellulose, D-mannitol, paracetamol and magnesium stearate) was experimentally evaluated. To this end, powder materials were let to flow over the stainless-steel pipes of the GranuCharge™ instrument. The resulting charge was compared to the one acquired during twin-screw feeding. In both cases, paracetamol exhibited the highest charging tendency followed by D-mannitol and microcrystalline cellulose and last by magnesium stearate. A good correlation was found for charge values obtained for both methods, despite the different tribo-charging mechanisms involved in the two set-ups. However, these differences in experimental set-ups led to diverse magnitudes and, in one case, polarity of charge. Additionally, an extensive material characterization was performed on the selected powders and results were statistically analyzed to identify critical material attributes (CMAs) affecting powder tribo-charging. A strong correlation was obtained between the measured charge and inter-particle friction. This indicated the latter as one of the most influencing material characteristic impacting the powder tribo-charging phenomenon of the selected materials.
Display omitted
We present our recent advancements in developing a viable manufacturing process for printed medicine. Our approach involves using a non-contact printing system that incorporates both ...piezoelectric- and solenoid valve-based inkjet printing technologies, to deliver both active and inactive pharmaceutical materials onto medical-graded orodispersible films. By using two complimentary inkjet technologies, we were able to dispense an extensive range of fluids, from aqueous drug solutions to viscous polymer coating materials. Essentially, we demonstrate printing of a wide range of formulations for patient-ready, orodispersible drug dosage forms, without the risk of drug degradation by ink heating and of substrate damages (by contact printing). In addition, our printing process has been optimized to ensure that the drug doses can be loaded onto the orally dissolvable films without introducing defects, such as holes or tears, while retaining a smooth surface texture that promotes patient adherence and allows for uniform post-coatings. Results show that our platform technology can address key issues in manufacturing orodispersible drug dosage forms and bring us closer to delivering personalized and precision medicine to targeted patient populations.
Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has taken more than 1 million lives globally. This study, based on the official media ...releases of the Government of Nepal, analyses the clinical and epidemiological features of the individuals who died as a result of COVID-19 in Nepal from 23 January to 10 August 2020. We found that nearly half of the deaths were among people less than 50 years of age and being female increased the risk of death. The majority of deaths were associated with co-morbidities, the most common being cardiovascular diseases and diabetes followed by respiratory diseases. With the approaching festive season and relaxed lockdown, both government and citizens need to be more cautious about the severity of COVID-19 and take appropriate action.
Display omitted
This work evaluates several compositions of an amorphous solid dispersion (ASD) comprising nimodipine (NMD) as poorly soluble model API in a dual-polymer carrier system. HPMC E5 and ...Eudragit E were used for the two polymeric carriers. The formulation was designed for hot-melt extrusion (HME) and subsequent strand pelletization. The aim was to identify a formulation window with desired functional ASD performance, i.e. physical stability and immediate API release, as well as processability in strand pelletization. Samples were prepared using small-scale methods, such as vacuum compression molding (VCM) and benchtop extrusion. Miscibility and phase studies were performed for a wide range of polymer ratios and three levels of API content (10–30% w/w). Ternary ASD formulations were phase-separated, yet physically stable upon exposure to elevated temperature/humidity. A study of phase composition showed that the drug molecules were predominantly solubilized in the Eudragit E fraction of the formulation. The miscibility study and Fourier-transform infrared spectroscopy indicated hydrogen (H)bond interactions between NMD and Eudragit E. In HPMC, the amorphous API was dispersed in polymeric matrix and stabilized due to anti-plasticization and the disruption of intermolecular Hbonding between API molecules. Concerning processability in strand pelletization the formulation is limited at high Eudragit E content. NMD and EE-rich phases exhibit low mixture glass transition, low melt stability and brittle breaking behavior upon strand cutting. The high viscosity and yield point of HPMC contributes to the mechanical robustness of the strand at temperatures relevant for processing. Formulation-intrinsic dissolution rates in VCM ASDs developed as an irregular function of polymer ratio, associated with diverse and competitive dissolution mechanisms in the polymers. With regard to the binary system of NMD with HPMC E5, surface crystallization was observed in VCM ASDs. For extruded pellets this was not the case, and a steady trend of formulation-intrinsic dissolution rate across different polymer ratios was observed. These discrepancies indicated a major influence of shear stress during sample preparation on HPMC-based ASD performance. Finally, a feasible formulation window within a polymer ratio of 1:2–2:3 Eudragit E:HPMC was identified in which Eudragit E acts as a dissolution rate enhancer and ASD stabilizer during dissolution.
PDF
