Soft Gelatin Research Articles

Analysis of second-generation anti histamine fexofenadine soft gelatin capsules and its related compound by using RP-HPLC

Analysis of second-generation anti histamine fexofenadine soft gelatin capsules and its related compound by using RP-HPLC

3D bioprinting microgels to construct implantable vascular tissue

Engineered implantable functional thick tissues require hierarchical vasculatures within cell-laden hydrogel that can mechanically withstand the shear stress from perfusion and facilitate angiogenesis for nutrient transfer. Yet current extrusion-based 3D printing strategies are unable to recapitulate hierarchical networks, highlighting the need for bioinks with tunable properties. Here, we introduce an approach whereby crosslinkable microgels enhance mechanical stability and induce spontaneous microvascular networks comprised of human umbilical cord vein endothelial cells (HUVECs) in a soft gelatin methacryoyl (GelMA)-based bioink. Furthermore, we successfully implanted the 3D printed multi-branched tissue, being connected from the rat carotid artery to the jugular vein direct surgical anastomosis. The work represents a significant step toward in the field of large vascularized tissue fabrication and may have implications for the treatment of organ failure in the future.

Analysis of soft gelatin capsule with real-time polymerase chain reaction for halal autenthication

Halal medicine is an interesting topic to always discuss because it is a priority choice for Muslim consumers, one of which is halal capsules. Currently, molecular biology techniques such as real-time polymerase chain reactions are rapidly developing, including for the analysis of non-halal components based on DNA sequences. This study aimed to validate the quantitative PCR method for identifying DNA in gelatin-based products and to apply the confirmation method designed for capsule samples on the market circulating in Yogyakarta to prove the halalness of these samples. Validation of the porcine DNA detection analysis method on standard extraction of porcine gelatin using primer pairs obtained in previous studies. Validated methods are used for testing market capsule shells. The qPCR method using D-loop primers is specifically capable of amplifying porcine gelatin DNA up to a concentration of 0.5 pg/µL, with a CV value in the amplification response of porcine gelatin DNA isolates (1000 pg/µL) of 0.85% which meets the test criteria using the PCR. Three samples of commercial soft capsules tested gave a positive amplification response, meaning that the samples tested contained porcine DNA, and one negative sample, which probably had non-porcine gelatin. The application of this method is also very useful for ensuring the authenticity of the capsule shell, especially from cross-contamination and counterfeiting.

Harnessing matrix stiffness to engineer a bone marrow niche for hematopoietic stem cell rejuvenation.

Hematopoietic stem cell (HSC) self-renewal and aging are tightly regulated by paracrine factors from the bone marrow niche. However, whether HSC rejuvenation could be achieved by engineering a bone marrow niche exvivo remains unknown. Here, we show that matrix stiffness fine-tunes HSC niche factor expression by bone marrow stromal cells (BMSCs). Increased stiffness activates Yap/Taz signaling to promote BMSC expansion upon 2D culture, which is largely reversed by 3D culture in soft gelatin methacrylate hydrogels. Notably, 3D co-culture with BMSCs promotes HSC maintenance and lymphopoiesis, reverses aging hallmarks of HSCs, and restores their long-term multilineage reconstitution capacity. In situ atomic force microscopy analysis reveals that mouse bone marrow stiffens with age, which correlates with a compromised HSC niche. Taken together, this study highlights the biomechanical regulation of the HSC niche by BMSCs, which could be harnessed to engineer a soft bone marrow niche for HSC rejuvenation.

In vitro dissolution test of ketoprofene: development and evaluation of release from soft and hard gelatine capsules

Ketoprofen belongs to a group of widely used non-steroidal anti-inflammatory drugs (NSAIDs). It is found in several doses and various forms of medications. Therapeutic efficacy is related to the rate of release of the active substances, which depends on the formulation, the quality of the constituent substances and solubility. In order to determine the efficacy of drug products containing ketoprofen available on the pharmaceutical market in Poland, studies comparing the release profiles of the active substance contained in specific formulation and doses, Ketokaps MAX, 50 mg, soft capsules, Ketonal Active, 50 mg, hard capsules, Ketokaps MED, 100 mg, soft capsules, Refastin, 100 mg, film-coated tablets and Ketonal Forte, 100 mg, film-coated tablets have been conducted. Drug release has been tested using FaSSGF and FaSSIF bioequivalent media in a type IV flow apparatus. The results indicate that the product Ketokaps MAX, 50 mg has a shorter release time of ketoprofen and a faster reached maximum concentration of the released active substance than the market product Ketonal Active, 50 mg. The same outcomes will be achieved by the product Ketokaps MED, 100 mg compared to the market products Refastin, 100 mg and Ketonal Forte, 100 mg. In vitro studies confirm that the tested products differ noticeably in the kinetics of release of the active substance. Ketokaps MAX, 50 mg and Ketokaps MED, 100 mg achieve c max in a shorter time.

The effect of adding curcumin to sodium valproate in treatment of patients with bipolar disorder in the acute phase of mania: A randomized double-blind clinical trial.

Inflammatory processes play a role in the etiopathogenesis of bipolar disorder type 1. Full therapeutic responses are seldom seen and the ongoing inflammatory processes in the brain could lead to neuronal loss. Curcumin, a relatively safe herbal compound, has been shown to have anti-inflammatory effects. The present randomized double-blind clinical trial study aimed to investigate the effect of adding curcumin to the treatment regimen of BID. This randomized double-blind clinical trial was conducted on 78 patients diagnosed with BID according to the Diagnostic and Statistical Manual of Mental Disorders (DSM 5) criteria. The sample were divided into two groups. Patients in both groups received sodium valproate starting at a dose of 600 milligrams per day and administered up to 20 milligrams per kilogram per day or the highest dosage of the patient's tolerance. Patients in the intervention group also received curcumin as nanomicelle in soft gelatin capsules 40 milligrams per day. The control group received placebo tablets with the same characteristics as the curcumin tablets. They were assessed by a psychiatrist using the Young Mania Rating Scale (YMRS), Mini-Mental State Examination (MMSE), Clinical Global Impression (CGI), and a medication side effect questionnaire at the beginning of the study, as well as in the first, second, and fourth weeks of the study. Among the 78 patients chosen to participate in the project, 54 people completed the trial. No specific side effect was observed in the two groups. Both groups showed an increase in their MMSE scores compared to the beginning of the study (value of p < 0.001). Although this increase was not statistically different between the two groups (value of p = 0.68). The YMRS score of both groups decreased significantly by the end of the study (value of p < 0.001); however, this decrease was not significantly different between the two groups (value of p = 0.64). In addition, the two groups experienced a significant increase in their CGI scores throughout the study (value of p < 0.001), this increase however was not statistically different between the two groups (value of p = 0.88). The present study suggested that curcumin may not be a useful adjuvant agent in the management of patients with BID receiving sodium valproate as treatment.Clinical trial registration: Iranian Registry of Clinical Trials (IRCT), identifier IRCT2016102530504N1.

Extemporaneously compounded liquid formulations of clofazimine.

BACKGROUND: Clofazimine (CFZ) is routinely used worldwide for the treatment of leprosy and TB. However, no liquid or dispersible tablet formulations of CFZ are currently available commercially for patients with challenges ingesting soft gelatin capsules or solid formulations. The aim of this research was to develop stable extemporaneous liquid formulations of CFZ that can be stored at room temperature for several weeks to enable practical dosing in the field. METHODS: Two formulations were prepared in syrup and sugar-free vehicles with CFZ tablets using a simple method that can be used in a routine pharmacy. Suspensions were stored at room temperature and at 30°C for 30 days. Formulation aliquots were tested on Days 0, 15 and 30 for appearance, pH, potency and microbial counts. RESULTS: Appearance remained unchanged during storage. The pH of both formulations was between 4.0 and 6.0. Potency was between 90% and 110% for 30 days in the syrup formulation and for 15 days in the sugar-free formulation. Microbial counts met United States Pharmacopeia 1111 limits for oral aqueous liquids and specific organisms were absent. CONCLUSIONS: A simple field-friendly method was successfully developed for the preparation of CFZ liquid formulations using commonly available ingredients. This will permit practical dosing and titration for children and other patients with swallowing challenges.

Sodium bicarbonate for kidney transplant recipients with metabolic acidosis in Switzerland: a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial

Metabolic acidosis is common in kidney transplant recipients and is associated with declining graft function. Sodium bicarbonate treatment effectively corrects metabolic acidosis, but no prospective studies have examined its effect on graft function. Therefore, we aimed to test whether sodium bicarbonate treatment would preserve graft function and slow the progression of estimated glomerular filtration rate (GFR) decline in kidney transplant recipients. The Preserve-Transplant Study was a multicentre, randomised, single-blind, placebo-controlled, phase 3 trial at three University Hospitals in Switzerland (Zurich, Bern, and Geneva), which recruited adult (aged ≥18 years) male and female long-term kidney transplant recipients if they had undergone transplantation more than 1 year ago. Key inclusion criteria were an estimated GFR between 15 mL/min per 1·73 m2 and 89 mL/min per 1·73 m2, stable allograft function in the last 6 months before study inclusion (<15% change in serum creatinine), and a serum bicarbonate of 22 mmol/L or less. We randomly assigned patients (1:1) to either oral sodium bicarbonate 1·5-4·5 g per day or matching placebo using web-based data management software. Randomisation was stratified by study centre and gender using a permuted block design to guarantee balanced allocation. We did multi-block randomisation with variable block sizes of two and four. Treatment duration was 2 years. Acid-resistant soft gelatine capsules of 500 mg sodium bicarbonate or matching 500 mg placebo capsules were given at an initial dose of 500 mg (if bodyweight was <70 kg) or 1000 mg (if bodyweight was ≥70 kg) three times daily. The primary endpoint was the estimated GFR slope over the 24-month treatment phase. The primary efficacy analyses were applied to a modified intention-to-treat population that comprised all randomly assigned participants who had a baseline visit. The safety population comprised all participants who received at least one dose of study drug. The trial is registered with ClinicalTrials.gov, NCT03102996. Between June 12, 2017, and July 10, 2019, 1114 kidney transplant recipients with metabolic acidosis were assessed for trial eligibility. 872 patients were excluded and 242 were randomly assigned to the study groups (122 [50%] to the placebo group and 120 [50%] to the sodium bicarbonate group). After secondary exclusion of two patients, 240 patients were included in the intention-to-treat analysis. The calculated yearly estimated GFR slopes over the 2-year treatment period were a median -0·722 mL/min per 1·73 m2 (IQR -4·081 to 1·440) and mean -1·862 mL/min per 1·73 m2 (SD 6·344) per year in the placebo group versus median -1·413 mL/min per 1·73 m2 (IQR -4·503 to 1·139) and mean -1·830 mL/min per 1·73 m2 (SD 6·233) per year in the sodium bicarbonate group (Wilcoxon rank sum test p=0·51; Welch t-test p=0·97). The mean difference was 0·032 mL/min per 1·73 m2 per year (95% CI -1·644 to 1·707). There were no significant differences in estimated GFR slopes in a subgroup analysis and a sensitivity analysis confirmed the primary analysis. Although the estimated GFR slope did not show a significant difference between the treatment groups, treatment with sodium bicarbonate effectively corrected metabolic acidosis by increasing serum bicarbonate from 21·3 mmol/L (SD 2·6) to 23·0 mmol/L (2·7) and blood pH from 7·37 (SD 0·06) to 7·39 (0·04) over the 2-year treatment period. Adverse events and serious adverse events were similar in both groups. Three study participants died. In the placebo group, one (1%) patient died from acute respiratory distress syndrome due to SARS-CoV-2 and one (1%) from cardiac arrest after severe dehydration following diarrhoea with hypotension, acute kidney injury, and metabolic acidosis. In the sodium bicarbonate group, one (1%) patient had sudden cardiac death. In adult kidney transplant recipients, correction of metabolic acidosis by treatment with sodium bicarbonate over 2 years did not affect the decline in estimated GFR. Thus, treatment with sodium bicarbonate should not be generally recommended to preserve estimated GFR (a surrogate marker for graft function) in kidney transplant recipients with chronic kidney disease who have metabolic acidosis. Swiss National Science Foundation.

Tomographic volumetric bioprinting of heterocellular bone-like tissues in seconds.

Tomographic volumetric bioprinting (VBP) has recently emerged as a powerful tool for rapid solidification of cell-laden hydrogel constructs within seconds. However, its practical applications in tissue engineering requires a detailed understanding of how different printing parameters (concentration of resins, laser dose) affect cell activity and tissue formation. Herein, we explore a new application of VBP in bone tissue engineering by merging a soft gelatin methacryloyl (GelMA) bioresin (<5kPa) with 3D endothelial co-culture to generate heterocellular bone-like constructs with enhanced functionality. To this, a series of bioresins with varying concentrations of GelMA and lithium Phenyl(2,4,6-trimethylbenzoyl)phosphinate (LAP) photoinitiator were formulated and characterized in terms of photo-reactivity, printability and cell-compatibility. A bioresin with 5% GelMA and 0.05% LAP was identified as the optimal formulation for VBP of complex perfusable constructs within 30s at high cell viability (>90%). The fidelity was validated by micro-computed tomography and confocal microscopy. Compared to 10% GelMA, this bioresin provided a softer and more permissive environment for osteogenic differentiation of human mesenchymal stem cells (hMSCs). The expression of osteoblastic markers (collagen-I, ALP, osteocalcin) and osteocytic markers (podoplanin, Dmp1) was monitored for 42 days. After 21 days, early osteocytic markers were significantly increased in 3D co-cultures of hMSCs with human umbilical vein endothelial cells (HUVECs). Additionally, we demonstrate VBP of a perfusable, pre-vascularized model where HUVECs self-organized into an endothelium-lined channel. Altogether, this work leverages the benefits of VBP and 3D co-culture, offering a promising platform for fast scaled biofabrication of 3D bone-like tissues with unprecedented functionality. STATEMENT OF SIGNIFICANCE: This study explores new strategies for ultrafast bio-manufacturing of bone tissue models by leveraging the advantages of tomographic volumetric bioprinting (VBP) and endothelial co-culture. After screening the properties of a series of photocurable gelatin methacryloyl (GelMA) bioresins, a formulation with 5% GelMA was identified with optimal printability and permissiveness for osteogenic differentiation of human mesenchymal stem cells (hMSC). We then established 3D endothelial co-cultures to test if the heterocellular interactions may enhance the osteogenic differentiation in the printed environments. This hypothesis was evidenced by increased gene expression of early osteocytic markers in 3D co-cultures after 21 days. Finally, VBP of a perfusable cell-laden tissue construct is demonstrated for future applications in vascularized tissue engineering.

Biosynthesis and pharmacokinetics of Panax notoginseng enteric-coated soft capsules.

To investigate the biosynthesis and pharmacokinetic course of enteric-coated soft capsules of Panax notoginseng saponins (PNS) in a beagle dog model. To satisfy the enteric properties of soft capsules, the PNS enteric soft gelatin capsules were prepared by formaldehyde impregnation and orthogonal experimental design. The fluidity of gelatin and the disintegration time were selected as evaluation indexes; the soft gelatin capsule content was self-emulsifying, and the Km value and the optimal prescription were determined by making three-phase diagrams; in vivo pharmacokinetics studies were performed on six beagle dogs with 3 dogs in each group. Beagle dogs were divided into two groups randomly. One group was given PNS self-emulsifying enteric capsule and the other was given market conventional capsules. Plasma samples were collected at different times. After 1 week, the crossover experiment was carried out. The plasma concentration was detected by HPLC-MS (high performance liquid chromatography-mass spectrometry). Then the pharmacokinetic parameters were calculated by non-compartment model analysis. The range and variance analysis of the orthogonal test determined that the best prescription of total saponins of Panax notoginseng enteric soft capsule was:gelatin:glycerol:water =1:1:2, Soak the films in 1% formaldehyde for 1 hour. The contents of the soft capsule self-microemulsion are prescribed as: IPM (isopropyl myristate):Cremophor RH40:PEG400 (polyethylene glycol 400) =1:4.5:4.5 (with suitable PNS); the pharmacokinetic parameters of PNS self-emulsified enteric capsules and conventional capsules in the market are as follows: Rb1:Cmax is (18.05±0.26) and (15.50±0.51) ng/mL, Tmax is (2.00±0) and (3.00±0) h, AUC0→t is 98.49±1.16 and 34.46±2.02 (ng/mL)·h, relative bioavailability is 196.2%; Rg1: Cmax is 4.16±0.25 and 3.88±0.28 ng/mL, Tmax is 2.00±0 and 1.50±0 h, area under drug time curve (AUC)0→t is 11.80±2.93 and 10.45±2.29 (ng/mL)·h, relative bioavailability is 77.2%; R1:Cmax is 1.84±0.25 and 1.48±0.21 ng/mL, Tmax is 2.08±0.49 and 1.92±0.20 h, AUC0→t is 7.06±2.07 and 7.16±2.59 (ng/mL)·h, relative bioavailability is 117.7%. The experiment in vivo showed the higher relative bioavailability of PNS self-emulsifying enteric capsule compared with market conventional capsules. This will provide a potential application prospect for the clinical research and applications of PNS.

The effect of Ni gella sativa and vitamin D3 supplementation on the clinical outcome in COVID-19 patients: A randomized controlled clinical trial.

Background: The coronavirus disease 2019 (COVID-19) is a novel coronavirus that causes severe infection in the respiratory system. Since the immune status plays an essential role in combating COVID-19, herbal medicines, which have an immunomodulatory effect, may help prevent and even treat COVID-19. Nigella sativa is one of the herbal medicines with antiviral and immunomodulatory activities, and its therapeutic effectiveness makes it a promising add-on therapy for COVID-19. In addition, vitamin D3 has an immunomodulatory role, but the effect of therapeutic vitamin D3 supplementation in SARS-CoV-2 infection is still not well-known. Objective: This study aims to investigate the effects of Nigella sativa and vitamin D3 as single supplemental therapies and in combination on viral clearance indicated by a negative polymerase chain reaction and the alleviation of symptoms during the study follow-up duration of 14days. Patients and Methods: The study design was an open-label randomized controlled clinical trial conducted at the Respiratory Hospital at the Kobry El Qobba Armed Forces Medical Complex. In total, 120 COVID-19 patients with mild to moderate symptoms were randomly assigned to four groups, with thirty patients each, as follows: Group 1 received an oral dose of 900mg Nigella sativa through 450mg soft gelatin capsules twice daily for two weeks; Group 2 received 2,000 IU of vitamin D3 through 1000-IU tablets given as two tablets, once daily; Group 3 received 900mg of Nigella sativa and 2,000 IU of vitamin D3 in the same manner of dosing as in the previous groups; and Group 4 was the control group. All groups received standard therapy for COVID-19 infections and clinical management of COVID-19's clinical symptoms. Results: The Nigella sativa-vitamin D3 combination in addition to the standard therapy for COVID-19 infections significantly contributed to the alleviation of most COVID-19 symptoms: 50% of patients were free of cough after 7days, 70% showed an absence of fatigue after 4days, 80% had no headache after 5days, 90% were free of rhinorrhea after 7days, and 86.7% of the patients had no dyspnea after 7days. Moreover, patients in the four studied groups showed a reduced median temperature after 3days of treatment. Negative results of the polymerase chain reaction (PCR) test recorded on the 7th and 14thday of therapy were superior in the Nigella sativa and vitamin D3 combination arm compared to those of the other studied arms where the value of the odds ratio (OR) on the 7thday was 0.13 with 95% CI: 0.03-0.45 and that of the 14th day was 0.09 with 95% CI: 0.02-0.3. Conclusion: The results of this study showed a promising therapeutic benefit of the administration of Nigella sativa and vitamin D3 combination in COVID-19 patients with mild to moderate symptoms. Additionally, the remarkable viral clearance in a short time interval and reduction in the severity and progression of symptoms recommended the use of this combination as an add-on therapy for the management of COVID-19 patients. Clinical Trial Registration: ClinicalTrials.gov, Identifier: NCT04981743.

An open-label, randomized, crossover study to evaluate the bioavailability of nanoemulsion versus conventional fat-soluble formulation of cholecalciferol in healthy participants

BackgroundNanoemulsion preparations of cholecalciferol available in the market claim to have better bioavailability than the conventional fat-soluble cholecalciferol. However, limited data are available in humans for such preparations. We, therefore, compared the relative bioavailability of two formulations of 60,000 IU cholecalciferol (nanoemulsion oral solution, water-miscible vitamin D3 [test] vs soft gelatin capsules [reference]) in healthy adult participants. MethodsIn this randomized, open-label, two sequence, single-dose, two-way crossover study (CTRI/2018/05/013839), Indian participants aged 18–45 years received single dose of nanoemulsion and capsule formulations, under fasting conditions. Blood samples collected over 120 h were assessed to determine cholecalciferol concentrations. Pharmacokinetic parameters (area under the concentration-time curve up to 120 h [AUC0–120h], maximum observed drug concentration [Cmax], time to reach maximum drug concentration [Tmax], terminal half-life [T½el], and terminal elimination rate constant [Kel]) were estimated using baseline corrected data and analyzed using analysis of variance. ResultsAmong the 24 eligible participants, the relative bioavailability of nanoemulsion was significantly higher than the capsules by 36% (p = 0.0001) based on AUC0–120h. Similarly, Cmax of the nanoemulsion was significantly higher by 43% (p = 0.0001) than that of the capsules. The intra-participant variability for AUC0–120h and Cmax were 23.22% and 26.51%, respectively. The Tmax, T½el, and Kel were comparable for both the formulations. No adverse effects were noted with either of the two formulations. ConclusionsNanoemulsion oral solution of cholecalciferol showed a greater bioavailability compared with soft gelatin capsules, under fasting conditions, in healthy human participants.

Non-Conventional Time Domain (TD)-NMR Approaches for Food Quality: Case of Gelatin-Based Candies as a Model Food.

The TD-NMR technique mostly involves the use of T1 (spin-lattice) and T2 (spin-spin) relaxation times to explain the changes occurring in food systems. However, these relaxation times are affected by many factors and might not always be the best indicators to work with in food-related TD-NMR studies. In this study, the non-conventional TD-NMR approaches of Solid Echo (SE)/Magic Sandwich Echo (MSE) and Spin Diffusion in food systems were used for the first time. Soft confectionary gelatin gels were formulated and conventional (T1) and non-conventional (SE, MSE and Spin Diffusion) TD-NMR experiments were performed. Corn syrups with different glucose/fructose compositions were used to prepare the soft candies. Hardness, °Brix (°Bx), and water activity (aw) measurements were also conducted complementary to NMR experiments. Relaxation times changed (p < 0.05) with respect to syrup type with no obvious trend. SE/MSE experiments were performed to calculate the crystallinity of the samples. Samples prepared with fructose had the lowest crystallinity values (p < 0.05). Spin Diffusion experiments were performed by using Goldman–Shen pulse sequence and the interface thickness (d) was calculated. Interface thickness values showed a wide range of variation (p < 0.05). Results showed that non-conventional NMR approaches had high potential to be utilized in food systems for quality control purposes.

Atazanavir-Concentrate Loaded Soft Gelatin Capsule for Enhanced Concentration in Plasma, Brain, Spleen, and Lymphatics.

This study investigates the development of atazanavir-concentrate loaded soft gelatin capsule for achieving enhanced atazanavir (ATV) concentration in plasma, brain, spleen, and lymphatics beneficial in the significant reduction of viral load in HIV infection. For this purpose, ATV-concentrate in the presence and absence of Soluplus with corn oil, oleic acid, tween 80, and propylene glycol was developed. The developed ATV-concentrate was found to have enhanced dispersibility with no signs of precipitation after dilution with simulated G.I fluid as evident from particle size (16.49±0.32 nm) and PDI (0.217±0.02) analysis. The rheological and molecular docking studies explainedthe reduction of viscosity of SuATV-C due to the intermolecular H-bond between ATV and Soluplus that helps to retard crystallization. The shell of the soft gelatin capsule retains its integrity when subjected to a folding endurance test on a texture analyzer depicting that the concentrate did not affect the integrity of the soft gelatin capsule shell. An ex vivo and in vivo pharmacokinetic study in rats revealed that the SuATV-C soft gelatin capsule (SuATV-C SGC) indicated 2.9 fold improvement in rate and extent of permeation and absorption than that of ATV-suspension. The tissue distribution study also exhibited higher drug concentration in the brain (2.5 fold), lymph nodes (2.7 fold), and spleen (1.2 fold) administered with SuATV-C SGC, revealing the overwhelming influence of Soluplus and corn oil. In a nutshell, these studies demonstrated that SuATV-C SGC seems to have the potential to deliver an anti-retroviral drug to the viral sanctuaries for the better management of HIV.

A practical method for oral administration of isotretinoin in pediatric oncology patient: A case study of neuroblastoma.

Isotretinoin is a synthetic vitamin A derivative, administered off-label as maintenance therapy for neuroblastoma. This report addresses the challenge of administering isotretinoin to children, given its availability as soft gelatin capsules only. A 3-year-old boy diagnosed with stage IV neuroblastoma has undergone multimodal therapy, including six cycles of chemotherapy, followed by tumor resection and radiotherapy. Later, he was initiated on immunotherapy and prescribed isotretinoin 50 mg orally twice daily for two weeks, before each immunotherapy cycle. Isotretinoin is not available in liquid formulation and the patient could not swallow isotretinoin capsules. Therefore, pharmacist counseling was required to ensure appropriate administration of the drug. The patient's parents were instructed to pierce prescribed capsules, and empty and dilute their contents into a small glass containing olive oil after taking safety measures. Isotretinoin's stability in olive oil for 72 h was compared using high-performance liquid chromatography to its stability in soybean oil. The recovery rates were 98.62% and 98.3%, respectively. Drug miscibility was not an issue as isotretinoin is lipophilic. Therefore, it could be administered easily without considerable remaining on the interior wall of the glass. To the best of our knowledge, this is the first report that suggests a practical method for administering isotretinoin in liquid form, particularly in pediatric oncology patients. Isotretinoin was noted to be stable in olive oil and its exposure to light and oxygen would not be an issue given the short time from preparation to administration and the low emphasis on exposure by the manufacturer when such a method is recommended.

Preparation and Characterization of Clopidogrel Bisulfate-hydroxypropyl-β-Cyclodextrin Mixed Inclusion Complex for Improved Intestinal Solubility and Anti-Thrombotic Efficacy

The study aimed to increase the intestinal solubility and absorption of orally bioavailable clopidogrel-bisulfate (CPB) by complexing with hydroxypropyl-β-cyclodextrin (HCD) to form a binary inclusion complex that was stabilized by Tween 80 (T80) resulting into mixed inclusion complex. The results of phase solubility studies and molecular docking of CPB with β-cyclodextrin (β-CD) and HCD suggested higher solubility and binding energy of the stable CPB: HCD complex in the presence of T80 as compared to the CPB: β-CD complex. The D-Optimal mixture design was used to optimize the formulation containing the CPB: HCD: T80 mixed inclusion complex. The results suggest the enhanced stability of the CPB: HCD inclusion complex in the presence of T80. The spectral attributes confirmed the inclusion complexation and pointed out the central position of CPB in a hydrophilic cavity of HCD. Further, the prepared soft gelatin capsule successfully confirmed the importance of obliterating the intestinal precipitation associated problem of CPB through an in-vitro release study. The anticoagulant activity in rabbits confirmed that soft gelatin capsules showed 1.2 folds and 1.3 folds increase in clotting time, 1.2 fold and 1.5 folds increase in bleeding time when compared to marketed formulation and pure drug, respectively. Conclusively, soft gelatin capsules exhibit the potential to enhance the oral bioavailability of CPB, leading to reduction of the dose and dose-related side effects.

Soft Tunable Gelatin Robot with Insect-like Claw for Grasping, Transportation, and Delivery

Soft Tunable Gelatin Robot with Insect-like Claw for Grasping, Transportation, and Delivery

Formulation and Physicochemical and Biological Characterization of Etoposide-Loaded Submicron Emulsions with Biosurfactant of Sophorolipids.

Etoposide (ETO), a traditional anticancer chemotherapeutic agent, is commercialized in oral soft gelatin capsules and non-aqueous parenteral solutions form. Novel formulation application and new excipients exploration are needed to improve the water-solubility and comfort of the drug administration. In the present study, novel etoposide-loaded submicron emulsions (ESE) with the biosurfactants of acidic sophorolipid (ASL) and lactonic sophorolipid (LSL) instead of the chemical surfactant of Tween-80 were prepared and characterized. Firstly, parameters of medium-chain triglyceride: long-chain triglyceride (MCT:LCT), lecithin concentration, homogenization pressure and cycle, and type and concentration of surfactants were investigated to optimize the formation of ESEs. Then the physicochemical properties, antitumor activity, stability, and security of ESEs were compared. The results showed that ASL performed the best properties and activities than Tween-80 and LSL in ESE formation. ASL-ESE showed higher drug loading capacity, slower release rate, and significantly increased antitumor activity against ovarian cancer cell line A2780 via apoptosis than Tween-ESE and commercial ETO injection. Besides, both ASL-ESE and Tween-ESE caused no hemolysis, and the safe dose of ASL was 2.14-fold that of Tween-80 in the hemolysis test, making ASL more reliable for drug delivery applications. Furthermore, ASL-ESE exhibited equivalent long-term and autoclaving stability to Tween-ESE. These results thus suggested the excellent competences of ASL in ESE formation, efficacy enhancement, and safety improvement.

Medication-administration-via-enteral-feeding-tubes-a-survey-of-nurses-knowledge-and-practice

Introduction: Enteral feeding is a type of nutritional support for critically ill patients who are unable to tolerate oral feeding. It is vital to ensure that nurses practise proper administration techniques via enteral feeding tubes (EFT) to ensure that medications can be delivered safely and effectively. Objective: This study aims to assess the knowledge and practice of nurses on medication administration through EFT. The association between demographics and knowledge was also explored. Method: This study is a cross-sectional, self-administered, content-validated, pre-tested questionnaire survey involving all nurses who worked in the ward setting at Hospital Queen Elizabeth II from August to December 2020. Result: A total of 409 questionnaires were sent out with 252 responses received. The majority of respondents were female (n = 240, 95.6%) with a median working experience of 84 months (interquartile range of 44 months). Most nurses knew that the immediate-release dosage forms (n = 237, 94.4%) may be crushed and administered through EFT. Similarly, most nurses were aware that sublingual nitroglycerin (GTN) tablets should not be crushed (n = 232, 92.8%) and that nystatin suspension should not be administered via EFT (n = 212, 85.1%). However, about half of the nurses responded incorrectly when questioned about the particulars of EFT involving the administration of sustained-release medications (n = 152, 60.6%), soft gelatin capsules (n = 111, 44.4%) and hard gelatin capsules (n = 102, 40.6%). Meanwhile, in terms of practice, a majority of the nurses would correctly routinely flush the EFT before (n = 226, 90.4%) and after (n = 245, 98.8%) the administration of medications. However, only a small proportion of nurses (n = 43, 17.3%) demonstrated the appropriate practice of administering all medications separately all the time. Furthermore, it was also worth noting that for some specific knowledge-based questions, nurses from the intensive care setting had more correct responses when compared to those from the general ward setting (p < 0.05). Conclusion: The knowledge gap and inconsistencies in practices amongst nurses related to the use of EFT may lead to suboptimal delivery of medications, whilst potentially compromising patient outcomes. Hence, continuous educational programs should be carried out to ensure safe and effective drug administration through EFT.

Viscoelastic Characterization of Soft Tissue-Mimicking Gelatin Phantoms using Indentation and Magnetic Resonance Elastography

Viscoelastic Characterization of Soft Tissue-Mimicking Gelatin Phantoms using Indentation and Magnetic Resonance Elastography