Demonstration of pharmaceutical tablet coating process by injection molding technology

We demonstrate the coating of tablets using an injection molding (IM) process that has advantage of being solvent free and can provide precision coat features. The selected core tablets comprising 10% w/w griseofulvin were prepared by an integrated hot melt extrusion-injection molding (HME-IM) process. Coating trials were conducted on a vertical injection mold machine. Polyethylene glycol and polyethylene oxide based hot melt extruded coat compositions were used. Tablet coating process feasibility was successfully demonstrated using different coating mold designs (with both overlapping and non-overlapping coatings at the weld) and coat thicknesses of 150 and 300?μm. The resultant coated tablets had acceptable appearance, seal at the weld, and immediate drug release profile (with an acceptable lag time). Since IM is a continuous process, this study opens opportunities to develop HME-IM continuous processes for transforming powder to coated tablets.     

Research hotspot and trend of microneedles in biomedical field: A bibliometric analysis from 2011 to 2020

BackgroundMicroneedles composed of arrays of micro-sized needles assembled on a patch, has attracted increasing interest in transdermal drug delivery due to its ease of use and lack of painful responses. Here, a bibliometric analysis was conducted to determine a hotspot and trend of microneedles in the biomedical field.MethodsAll relevant articles about microneedles between 2011 and 2020 were obtained from the databases of Web of Science (WOS) and PubMed of the National Center for Biotechnology Information (NCBI). A series of software such as VOSviwewer, the online bibliometric analysis website, CiteSpace, BICOMB and gCLUTO were used to process the data and get visual images. Processed data and visualized images were conducted to predict the trend of this research field.ResultsThe number of articles published over the last decade had increased rapidly (37 in 2011, 165 in 2020), the Journal of Controlled Release was the most productive journal in microneedle studies. The United States was the most productive country, while the Queens Univ Belfast topped the other institutions. Ryan F Donnelly was the most productive author in the field, while the two most cited articles were published by Gu Zhen group. More importantly, the research trend of microneedles had ranged from physicochemical properties and pharmacokinetics to insulin transdermal injection and vaccine development over the past decade. The four hot spots in microneedle studies, including skin rejuvenation, vaccines, fabrication technology and insulin delivery, were identified. Microneedle vaccination shows promising application prospects, and polymers are considered as the most promising materials for microneedles manufacturing.ConclusionsThis study will help researchers understand the hot spots and trends of microneedles in the biomedical field accurately and quickly. Moreover, the exploitation of novel polymeric microneedles will be a solid direction for subsequent research and development of transdermal drug delivery.     

Effect of binders on the release rates of direct molded verapamil tablets using twin-screw extruder in melt granulation

Conventional manufacturing of pharmaceutical tablets often involves single processes such as blending, granulation, milling and direct compression. A process that minimizes and incorporates all these in a single continuous step is desirable. The concept of omitting milling step followed by direct-molding of tablets utilizing a twin-screw extruder in a melt granulation process using thermoplastic binders was explored. The objective of this study was to investigate the effect of combining hydrophilic binder (HPMC K4M, PEO 1M), and hydrophobic binder (Compritol^® ATO 888, Precirol^® ATO 5) on the release profiles of direct-molded tablets and direct-compressed tablets from milled extrudates using a quality-by-design approach. It was identified that hydrophilic binder type and process significantly affects (p = 0.005) the release profiles of verapamil. Moreover, two-way interaction analysis demonstrated that the combination of process with type of hydrophilic polymer (p = 0.028) and the type of hydrophilic polymer with polymer ratio (p = 0.033) significantly affected the release profiles. The formulation release kinetics correlated to Higuchi release model and the mechanism correlated to a non-Fickian release mechanism. The results of the present study indicated that direct-molded tablets with different release profiles can be manufactured without milling process and through a continuous melt granulation using twin-screw extruder with appropriate thermoplastic binder ratio.     

Residence time modeling of hot melt extrusion processes

The hot melt extrusion process is a widespread technique to mix viscous melts. The residence time of material in the process frequently determines the product properties. An experimental setup and a corresponding mathematical model were developed to evaluate residence time and residence time distribution in twin screw extrusion processes.The extrusion process was modeled as the convolution of a mass transport process described by a Gaussian probability function, and a mixing process represented by an exponential function. The residence time of the extrusion process was determined by introducing a tracer at the extruder inlet and measuring the tracer concentration at the die. These concentrations were fitted to the residence time model, and an adequate correlation was found. Different parameters were derived to characterize the extrusion process including the dead time, the apparent mixing volume, and a transport related axial mixing. A 2³ design of experiments was performed to evaluate the effect of powder feed rate, screw speed, and melt viscosity of the material on the residence time. All three parameters affect the residence time of material in the extruder.In conclusion, a residence time model was developed to interpret experimental data and to get insights into the hot melt extrusion process.     

Seasonal variations in HbA1c among type 2 diabetes patients on a semi-arid climate between the years 2005–2015

AimsTo investigate the seasonal variations of HbA1c values in a semi-arid climate among type 2 diabetic patients throughout 11 years of care.MethodsA retrospective cohort study of 2860 patients with 61,187 HbA1c measures. We calculated the averages of HbA1c values of all patients and sub-groups defined by age, gender, BMI, ethnicity, insulin use, smoking status and region of residence, matched to the mean temperature and diurnal range over the 30 and 60 days prior to the HbA1c test date.ResultsWe found a sinusoidal seasonal pattern with statistically significant HbA1c levels gaps between the spring peak and the autumn trough (F = 18.4, P < 0.001). The lowest values were in October-November and the highest in March or August with a difference of 0.17–0.31% (2–4 mmol/mol). We found different relations between the mean temperature and HbA1c depending on season, gender, age, ethnicity and smoking habits.ConclusionThe study identified specific subgroups in which the seasonal influence is particularly marked. A possible explanation is that during hot periods people tend to change their diet and decrease their physical activity, effecting indirectly diabetic imbalance. Recognition of the seasonal variations of HbA1c levels in this geographical region could help physicians with diabetes care and HbA1c control.     

Crime displacement in digital drug markets

Background Crackdowns on urban sites with concentrated criminal activity are sometimes followed by geographical relocation of crime. Is this also the case in cyberspace, where illegal websites and online networks can be wiped clean, but also quickly rebuilt and replaced on new servers and URLs?Methods I address this question in three steps. First, I measure MDMA trade in a large digital market for drugs, before and after the arrest of a leading MDMA seller in the same market. Second, I count the number of available digital drug markets and vendor shops in the period February 2014–June 2018, to see if websites closed by police were replaced by new ones. Third, I track the digital movement and trading activities of individual drug sellers, before and after law enforcement shut down two large markets.Results After police arrested a leading MDMA seller, other MDMA sellers filled most – but not all – of the gap. A major law enforcement crackdown reduced the number of available markets, but new ones were created, and market counts eventually surpassed the previous peak. When law enforcement shut down two big markets, many of the sellers relocated to other e-commerce sites and continued high-earning operations there.Conclusion Arrests and market closures redirect digital drug trade to other sellers and markets. Hot spot policing in cyberspace might produce temporary results, but is arguably ineffective in the long run, as actors use information and communication technology’s unique capacities to reorganize.     

Self-compassion weakens the association between hot flushes and night sweats and daily life functioning and depression

Objectives

Some women find hot flushes and night sweats (HFNS) to interfere more in daily life and mood than others. Psychological resources may help to explain these individual differences. The aim of this study was to investigate the role of self-compassion, defined as healthy way of relating toward the self when dealing with difficult experiences, as a potential moderator of the relationship between HFNS and daily life activities, which in turn influences symptoms of depression.

Study design

This was a cross-sectional study using questionnaire data from 206 women aged 40–60 who were currently experiencing hot flushes and/or night sweats. Path analysis was used to model relationships among menopausal factors (HFNS frequency and daily interference ratings), self-compassion and mood.

Main outcome measure

Hot flush interference in daily activities and depressive symptoms.

Results

On average, women experienced 4.02 HFNS per day, and HFNS frequency was moderately correlated with interference ratings (r = 0.38). In the path analytic model, self-compassion made significant direct contribution to hot flush interference ratings (β = −0.37) and symptoms of depression (β = −0.42), and higher self-compassion was associated with lower interference and depressive symptoms. Self-compassion also moderated the relationship between HFNS frequency and hot flush interference. Higher self-compassion was associated with weaker effects of HFNS frequency on daily interference.

Conclusions

Self-compassion may weaken the association between HFNS and daily life functioning, which in turn, could lead to less HFNS-related mood problems. These findings imply that self-compassion may be a resilience factor to help women manage hot flushes and night sweats.     

Stellate ganglion blockade and verbal memory in midlife women: Evidence from a randomized trial

ObjectivesIn a pilot randomized clinical trial of active stellate ganglion blockade (SGB) versus sham control, SGB significantly reduced the frequency of reported moderate to severe vasomotor symptoms (VMS) and the frequency of physiologic VMS measured using ambulatory skin conductance monitors. Here we examine secondary effects of SGB on verbal learning and memory.Study designIn a randomized, sham-controlled study, 36 women met eligibility criteria for cognitive assessments, of whom 17 were randomized to receive fluoroscopy-guided SGB and 19 to sham control.Main outcome measuresAt baseline and three months post-treatment, women completed tests of verbal learning and memory (primary outcome) and other cognitive measures and also wore an ambulatory monitor for 24 h to measure physiologic VMS and VMS reported in real time.ResultsVerbal learning improved following active SGB (p < 0.05) but not sham treatment; however, the interaction between group and time was not significant (p values 0.13-0.20). Two secondary cognitive measures improved only in the sham group. Improvements in physiologic VMS correlated significantly with improvements in verbal learning (r = 0.51, p < 0.05).ConclusionsSGB might confer benefits to memory in relation to the magnitude of improvement in physiologic VMS. Broadly these findings suggest a possible link between physiologic VMS and memory problems in midlife women.     

A 14-year-old girl who regained normal vision after bilateral visual impairment following hot water injury to the eyes

A 14-year-old girl presented with bilateral visual impairment following hot water injury to the eyes. The patient was admitted for a week and managed with guttae tropicamide 0.5% 8 h, diclofenac sodium 0.1% 4 h, and fluoroquinolone 0.3% 6 h and ointment chloramphenicol 8 h. Also, the patient was managed with capsule doxycycline 100 mg 12 h for 10 days, tablet cataflam 50 mg 12 h for 7 days and intramuscular tetanus toxoid 0.5 mg stat and dermacine cream for facial scald.The visual acuities improved from 3/60 (right eye) and 6/24 (left eye) to 6/6 in both eyes. There were resolutions of facial/eye pain, tearing, photophobia, lid edema, blepharospasm, and conjunctival hyperemia. There was complete healing of facial wounds and corneal ulcers. She was discharged from hospital on the 7th day of admission.Prompt presentation, degree of scald sustained, and appropriate medical intervention enhanced visual recovery and wound healing in the patient.