Gelatin Capsules Research Articles

A Stable Formulation of a Non-Steroidal Anti-inflammatory Drug, Ibuprofen and an Antihistamine drug, Famotidine for a Combination Therapy

Purpose: The present research study was focused on developing an oral dosage form with two highly incompatible drugs, a non-steroidal anti-inflammatory drug, Ibuprofen and an antihistamine drug, Famotidine to be administered as a combination therapy in a single dose and further asses the stability of the finished product. Methods: A novel drug formulation was designed by employing mini tablets technology to manufacture Famotidine core tablets and the core tablets are further film coated with Opadry II coating solution to inhibit Famotidine contact with Ibuprofen matrix. Film coated Famotidine 30 mg mini-tablets were then encapsulated in Ibuprofen blend to improve the compatibility and stability of the drug product [1,2]. Each mini-tablet of Famotidine contain 5 mg dose of Famotidine and 6 such mini-tablets were encapsulated in each size “00” hard gelatin capsule containing Ibuprofen blend equivalent to 800 mg claim. The stability of the finished product was evaluated in accelerated stability conditions to ensure the impurities are well within the Pharmacopeia (USP) assigned limits. Results: The dissolution release of Ibuprofen and Famotidine is higher than 85 % in 15 minutes and is compared against the only available product in the combination therapy, DUEXIS® (Ibuprofen and Famotidine Tablets 800 mg and 26.6 mg). The stability of the final formulation is evaluated by placing the samples in 40°C/75 % RH storage condition for six months and the results of the pharmacopeia (USP) listed specified and unspecified impurities are well not more than 0.5 % w/w of the label claim. Famotidine and Ibuprofen are two highly in-compatible drugs for a combination therapy, and has been a challenge in the field to formulate for a combination therapy to improve patient compliance. The two drugs tend to form impurities at significate levels in direct physical contact during any stage of the manufacturing process.

Efficacy of Levothyroxine Sodium Soft Gelatin Capsules in Thyroidectomized Patients Taking Proton Pump Inhibitors: An Open-Label Study.

Background: Treatment with proton pump inhibitors (PPIs) and antacids affects the gastrointestinal absorption of levothyroxine sodium (LT4) tablets. Patients with hypothyroidism taking LT4 and PPIs or antacids, thus, require appropriate monitoring. The objective of this study was to determine whether a soft gelatin capsule of LT4 (Tirosint®) would obviate the effect of PPIs on LT4 absorption. The objective was achieved by assessing the effects of a switch from a conventional LT4 tablet form to the same dose as soft capsules in thyroidectomized patients on treatment with LT4 and PPIs. Methods: Patients with history of hypothyroidism due to total thyroidectomy on stable treatment with LT4 tablets, and with gastrointestinal disease treated with PPIs, were switched to a 12-week treatment with Tirosint at the same dose of the LT4 tablets, while maintaining treatment with PPIs. Serum thyrotropin (TSH) levels were the primary endpoint of the study. Secondary efficacy endpoints were: serum levels of free thyroxine (fT4), total thyroxine (TT4), free triiodothyronine (fT3), total triiodothyronine (TT3), creatine-phosphokinase (CPK), sex-hormone binding globulin, ferritin, angiotensin converting enzyme, and a lipid panel. Results: Forty-seven patients (36 females and 11 males, mean age 55.4 years) were enrolled and 45 of them completed the study (2 patients withdrew consent). During treatment with Tirosint, mean TSH levels demonstrated a statistically significant decrease (mean changes from baseline: -0.32 mIU/L at week 6 and -0.68 mIU/L at week 12) and concomitant increases in thyroid hormone (TH) levels from baseline to week 12, which were statistically significant for fT3 and TT3 (mean changes from baseline: 0.26 pmol/L and 0.10 nmol/L, respectively). Significant decreases of serum low-density lipoprotein, total cholesterol, and CPK levels were observed at week 12. No signs/symptoms arose during the study that could be specifically correlated to either hypo- or hyperthyroidism. Conclusions: In thyroidectomized patients taking PPIs and replacement LT4, a switch from conventional LT4 tablets to LT4 soft capsules at the same dose was associated with a significant decrease in TSH and increase in TH, indicating that LT4 absorption may be less affected by PPIs when given in the form of soft capsules. Clinical Trial Registration: NCT03094416.

Gelatin medium for preserving of Trichinella spp. for quality control in laboratories - estimation of larvae viability.

Official food control laboratories ensure food safety using reliable, validated methods. Council Regulations (EC) No. 853/2004, 854/2004 and 882/2004 of the European Parliament established hygiene rules the production of food of animal origin, together with requirements for official controls. This leads to detailed requirements for Trichinella control set out in Commission Implementing Regulation (EU) 2015/1375 of 10 August 2015. These regulations require the laboratory to participate in proficiency testing (PT) to confirm their competence and improve the quality of testing, and require the PT Organizer to use methods for the preparation and preservation of parasite larvae in order to evaluate and improve detection. Traditional methods of preparing such larvae expose them to rapid degradation, making it necessary to simultaneously isolate the larvae and place them in meatballs to ensure quality. We developed a technique for preserving of Trichinella spp. for quality control such as PT sample preparation. The procedure protects larvae against toxic oxygen activity and bacterial destruction via a gelatin barrier. To estimate the viability of larvae preserved by this method, gelatin capsules with 10 larvae of T. spiralis in each were stored (4-8 °C) during 45 days of an experiment. Samples were tested at 2 day intervals (3 samples each day of testing). In total, 75 samples were tested. Larvae remained alive up to 3 weeks. The number of living larvae diminished after 27 days through day 43, after which no living larvae were observed. The gelatin medium procedure facilitated easy, high-throughput sample preparation and supported 100% recovery for 3 weeks. The method allows fast, efficient and accurate PT sample preparation.

Novel formulation of uncoated enteric capsule shells: Study the effect of gelling agents and salts on the rheology and physical properties

Currently, pharmaceutical technology offers new choices for protecting acid-sensitive substances from the stomach environment by dosage form of an enteric coating or the encapsulation of drugs in enteric capsules. Coating gelatin capsules is challenging, cost-intensive, and energy-consuming, as the smoothness of their surface hinders the adhesion of the film. In this study, the formulation of an uncoated gelatin-based enteric capsule shell composite is developed. The effect of four different gelling agents and six salts on the preparation of capsules is investigated. Potassium acetate (KAC) and κ-carrageenan are examined and selected as the best salt and gelling agent, respectively. The physicochemical, surface, and cross-section morphology, mechanical, and drug release properties of prepared enteric capsules (without (F1) and with (F2) gelatin) were characterized. The drug release of optimized capsules (F1, F2) was tested using pantoprazole. The results showed high stability (120 min) of prepared capsules in the stomach environment with no release (pH = 1.2), and then started to release in the intestinal medium (pH = 6.8) after 16 min, which is great according to the definition of the enteric capsule. Furthermore, the tensile strength of gelatin-based enteric capsules and pure gelatin capsules was tested and compared.

Development of Amlodipine Mini-tablets as a Polypill-component for the Personalized Therapy of Arterial Hypertension

Introduction. A personalized choice of antihypertensive combinations and doses is one of the promising trend in the field of combination therapy of arterial hypertension (AH). A polypill as a solid gelatin capsule with combination of mini-tablets can be used to realise this concept.Aim. Development of the composition and technology of Amlodipine 2,5 mg and 5 mg film-coated mini-tablets as a polypill-component for the personalized therapy of AH.Materials and methods. Active pharmaceutical ingredient (API) Amlodipine besylate (Glochem Industries Private Ltd., India) and excipients, such as diluent, disintegrant, lubricant, dye and premix for film coating, were used. Norvasc®, 5 mg tablets were used as a reference drug to estimate the release profile of Amlodipine. API and excipients were mixed in a «drunken barrel» mixer DGN-II (Shanghai Unique Machinery Technology Co., Ltd., China); mini-tablets were obtained on a DP30A laboratory automatic single-punch tablet press (Beijing Gylongli Sci. & Tech. Co., Ltd., China); film coatings on mini-tablets-cores were applied by using a BGB-1 laboratory machine (Chongqing Jinggong Pharmaceutical Machinery Co., Ltd., China). Assessment of technological characteristics of API and tablet mixtures and quality control of mini-tablets were conducted by the methods of State Pharmacopoeia of the Russian Federation XIV ed.Results and discussion. As a result of the study, the optimal composition of the excipients of the fillers group (lactose monohydrate, MCC and anhydrous calcium hydrogen phosphate in a ratio of 1 : 1 : 1) for the production of Amlodipine 2,5 mg and 5 mg mini-tablets-cores by direct compression was established. The technology of applying film coatings was developed. The equivalence of the release profiles of Amlodipine from the developed mini-tablets to the release profile of the reference drug was established.Conclusion. The composition and technology of Amlodipine 2,5 mg and 5 mg film-coated mini-tablets as a polypill-component for the personalized therapy of AH were developed.

185 Effects of a Lactobacillus Fermentation Product on the Fecal Characteristics, Fecal Microbial Populations, Immune Function, and Stress Markers of Adult Dogs

Abstract The objective of this study was to measure the effects of a Lactobacillus fermentation product (LBFP) on fecal characteristics and microbiota, blood biomarkers, immune function, and serum oxidative stress markers of adult dogs. Thirty adult beagle dogs [23 M, 7 F; mean age = 8.47 ± 2.65 y old; mean BW = 15.43 ± 4.17 kg] were used in a completely randomized design study. All dogs were fed a basal diet to maintain BW for 5 wk, followed by baseline blood and fecal sample collections. Dogs remained on the same diet, but then were randomly assigned to a placebo (dextrose) or LBFP supplement (both dosed at 4 mg/kg BW via gelatin capsule) for 5 wk (n = 15/treatment). Fecal and blood samples were collected at that time. Change from baseline data were analyzed using the Mixed Models procedure of SAS 9.4, with P < 0.05 being significant and P < 0.10 being trends. Most circulating metabolites and immunoglobulins (Ig) were unaltered by treatment, but LBFP-supplemented dogs had lower changes in serum corticosteroid isoenzyme of alkaline phosphatase (P < 0.05), alanine aminotransferase (P < 0.10), and IgM (P < 0.10) than controls. The change in fecal scores tended to be less (P = 0.068) in LBFP-supplemented dogs than controls, signifying firmer feces in LBFP-supplemented dogs. Regarding the fecal microbiota, alpha diversity indicators tended to be greater (P = 0.087) in LBFP-supplemented dogs than controls. One fecal bacterial phyla (Actinobacteriota) was altered by treatments, with its relative abundance tending to have a greater (P < 0.10) increase in controls than LBFP-supplemented dogs. Fifteen bacterial genera were altered (P < 0.05 or P < 0.10) by treatments, including relative abundances of fecal Peptoclostridium, Sarcina, and Faecalitalea that had a greater (P < 0.05) increase in controls than LBFP-supplemented dogs. In contrast, relative abundances of fecal Faecalibaculum, Bifidobacterium, and uncultured Butyricicoccaceae had a greater (P ≤ 0.05) increase in LBFP-supplemented dogs than controls. After wk 5, dogs underwent transport stress (45 min vehicle ride) to assess oxidative stress markers. The change in serum superoxide dismutase after transport had a greater (P < 0.0001) increase in LBFP-supplemented dogs than controls. Our data suggest that LBFP may provide benefits to dogs by stabilizing stool quality, beneficially shifting fecal microbiota, and protecting against oxidative damage when subjected to stress.

Comprehensive characterisation of tilapia fish gelatine under varied extraction conditions for the advancement of hard capsule production

SummaryHard capsules are a frequently used oral medication delivery form. This study aims to evaluate the potential of tilapia fish gelatine as a suitable material for hard capsules, by analysing various gelatine properties under different extraction temperatures (50, 60, 70, and 80 °C) and extraction periods (6 and 12 h). The results showed a range of values for the gelatine yield (22–33% (w/w)), gel strength (141–360 g), molecular weight distribution (140–300 kDa), and amino acid composition (185–220/1000 residues). FG70‐12 (296) and FG60‐6 (266) were found to have gel strength between 200 and 300 g thus suitable to be used as hard capsule material. Interestingly, the strongest gelatine having 360 g gel strength obtained from FG50‐6 (fish gelatine extracted at 50 °C for 6 h) became the essential ingredient for preparing hard capsules because two times dipping was enough to obtain the standard weight and thickness. A slight loss of moisture was identified during drying and rapid dissolution (4–8 min) detected from fish gelatine capsule at pH 6.8 or below. Therefore, hard capsules for pharmaceutical applications could be developed from fish gelatine as an alternative gelatine with similar properties as commercial hard capsules and satisfying the pharmacopoeia standard.

Oral meloxicam given as an ancillary treatment at respiratory disease diagnosis was not associated with growth, clinical scores, or ultrasound scores in preweaned dairy calves.

To assess the efficacy of a single dose of oral meloxicam as an ancillary therapy to an antibiotic given at the time of respiratory disease identification on average daily gain (ADG), behavioral attitude, clinical respiratory, and lung ultrasound scores in preweaned dairy calves. 215 male and female Holstein, Jersey, and crossbred preweaned calves enrolled between 1 and 14 days of age at study enrollment on a single commercial dairy in the western US. The study took place from March 4, 2021, to November 21, 2021. In this double-blind placebo-controlled study, calves were given an antibiotic (1.1 mL of tulathromycin/kg, SC, once) and either a placebo (1 mg of lactose monohydrate/kg, in a gelatin capsule) or oral meloxicam (1 mg/kg) at the time of respiratory disease identification. Behavioral attitude, clinical respiratory, and lung ultrasound scores and ADG were assessed in preweaned dairy calves at different time points including the next health examination, 1 week later, or at weaning. There was no association between treatment (placebo vs meloxicam) on ADG or respiratory disease status at weaning (P > .05). There was no effect of treatment on behavioral attitude, clinical respiratory, or lung ultrasound scores at the next health examination or 1 week later (P > .05). The present study did not provide evidence that oral meloxicam given once is beneficial for growth, behavioral attitude, or clinical or lung ultrasound scores.

Liquid and Pressure-Sensitive Adhesives Based on Cassava Starch and Gelatin Capsule Residue: Green Alternatives for the Packaging Industry

Natural polymer-based adhesives are green alternatives, necessary to reduce the problems impacted by synthetic adhesives. Starch and gelatin have extraordinary potential for the synthesis of biobased adhesives. Citric acid (CA), a natural acid, induces the crosslinking and hydrolyzing of both gelatin and starch. In this sense, this work deals with the use of gelatin capsule residues as a promising material to produce biobased adhesives in combination with cassava starch in the presence of different CA concentrations characterizing their mechanical, physicochemical and microstructural properties. Depending on CA concentration, formulations adjusted to different applications can be obtained such as liquid and pressure-sensitive adhesive films. The inclusion of CA allows us not only to improve the applicability of the system since it modifies the flowability of the adhesives as evidenced by the observed changes in the viscosity (from 158.3 to 90.3 for formulations with 20 and 80% CA, respectively). In addition, mechanical profiles showed that the inclusion of CA increased the adhesive bond strength (from 2230.7 to 2638.7 for formulations with 20 and 80% CA, respectively). Structural modifications induced by CA in adhesive formulations were highlighted by ATR-FTIR analysis.

Immunomodulating multivitamin complex and its role in antioxidant protection of the body

The article presents the results of experimental data on the development of an immunomodulatory multivitamin complex and the establishment of its role in the antioxidant defense of the body. The research objects were recipe ingredients, laboratory and industrial samples of the developed product. We used generally accepted and special methods for assessing the quality and safety of the developed product. The technology includes: preparation of raw materials, preparation of a mixture for encapsulation, encapsulation and sealing of capsules with gelatin, assessment of the quality of the resulting product. The composition of a new multivitamin composition with targeted antioxidant properties is given, mg / 1 capsule: red palm oil - 432; ascorbic acid - 70; ascorbate palmitate - 10; tocopherol acetate, 98% - 15.3 (vitamin E - 15); beta-carotene, 98% - 5.1 (beta - carotene - 0.5); silicon dioxide (carrier) - 17.6; gelatin capsule - 110. Total weight 660 mg. The functional properties of the developed product were assessed. The components of the developed product in the form of a multivitamin complex had a positive effect on the analyzed parameters of the SF-36 test. According to the test results, the general state of health in the group of volunteers after taking the multivitamin complex increased by 17.2%, while in the control group by only 9.5%, in terms of viability by 7.2 and 3.6% in the experimental and control groups respectively. The innovativeness of the new drug lies in the rejection of inert materials and the use as a carrier of a unique composition of red palm oil, rich, along with fat-soluble vitamins, highly active antioxidants - lycopene and coenzyme Q10. The proposed method of encapsulation in a protective gelatin capsule. This provides a fast action - a water-soluble and prolonged effect - of the fat-soluble fraction.

Shell Formulation in Soft Gelatin Capsules: Design and Characterization.

Soft gelatin capsules (SGCs)are the most widely used pharmaceutical form after tablets. The active components, active pharmaceutical ingredients (APIs), or nutrients are dissolved, dispersed, or suspended in a liquid or semisolid fill, which is covered with a gelatin shell. Several factors can modify the properties of the gelatin shell and subsequently affect their operative handling during manufacturing process and the stability of the soft gelatin capsules. Three elements appear to be crucial: the shell formulation (type and content of the different components such as gelatins-source, extraction method-plasticizers, or additives); the manufacture and storage conditions (temperature, humidity, light) as well as the interactions between fill-shell formulas. Mechanical and thermal analysis arise as straightforward but highly useful tools to monitor the properties of the gelatin shell. This review provides an updated overview on the shell formulation and design. Additionally, it presents the uses of mechanical and thermal techniques to characterize and evaluate the impact of different parameters on the gelatin behavior over the production and stability of these pharmaceutical forms. This will help to detect changes that are yet not visible by visual inspection ensuring a suitable finished product over its shelf-life.

Preliminary feasibility of a wrist-worn receiver to measure medication adherence via an ingestible radiofrequency sensor.

Adherence to medications is a complex task that requires complex biobehavioral support. To better provide tools to assist with medication adherence, digital pills provide an option to directly measure medication taking behaviors. These systems comprise a gelatin capsule with radiofrequency emitter, a wearable Reader that collects the radio signal and a smartphone app that collects ingestion data displays it for patients and clinicians. These systems are feasible in measuring adherence in the real-world, even in stigmatized diseases like HIV treatment adherence. While the current iteration of the digital pill system utilizes a wearable Reader worn like a necklace, preliminary feedback demonstrated that a miniaturized system that was worn on the wrist could be more functional in the real-world. This paper therefore describes the development and preliminary field testing of a wrist-borne wearable Reader to facilitate acquisition of oral HIV pre-exposure prophylaxis (PrEP) adherence data among individual prescribed PrEP.

WITHDRAWN: Gastroretentive fibrous dosage forms for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. Part 2: Experimental validation of the models of expansion, mechanical strength, and in vitro drug release

In Part 1, we have introduced gastroretentive fibrous dosage forms with expandable, strengthened excipient fibers, and drug-loaded inter-fiber space for prolonged delivery of sparingly soluble tyrosine kinase inhibitors. The in vitro expansion rate, post-expansion mechanical strength, and drug release rate were modeled for a dosage form containing 200 mg of nilotinib. In the present part, the dosage form was prepared and tested in vitro to validate the models. Upon immersing in a dissolution fluid, the fibrous dosage form expanded at a constant rate to a normalized radial expansion of 0.5 by 4 h, and then formed an expanded viscoelastic mass of high strength. The drug was released at a constant rate over a day. For comparison, a particle-filled gelatin capsule with the same amount of nilotinib disintegrated almost immediately, and released eighty percent of the drug content in just 10 min. The data validate the models of Part 1.

Cannabidiol Oil Ingested as Sublingual Drops or Within Gelatin Capsules Shows Similar Pharmacokinetic Profiles in Healthy Males.

Introduction: Cannabidiol (CBD) is a nonintoxicating phytocannabinoid used in clinical treatments and sold widely in consumer products. CBD products may be designed for sublingual or oral delivery, but it is unclear whether either is advantageous for CBD absorption. This study compared CBD pharmacokinetics after providing CBD oil as sublingual drops and within orally ingested gelatin capsules, at a dose relevant to consumer products. Materials and Methods: Eight males completed three conditions in a participant-blinded, randomized crossover design. Participants received the following combinations of placebo and CBD-containing (69 mg/mL) hemp oil in capsules and as sublingual drops: placebo capsules/placebo drops (Placebo), CBD capsules/placebo drops (CBD-Caps), and placebo capsules/CBD drops (CBD-Drops). Blood samples, blood pressure, and subjective scales were obtained/completed hourly for 6 h and at 24 h. Discussion: Plasma CBD concentrations were not different between CBD-Caps and CBD-Drops (interaction effect p=0.76). Peak CBD concentration (28.0±15.6 vs. 24.0±22.2 ng/mL), time of peak CBD concentration (4±1 vs. 4±2 h), and area under the concentration curve (45.3±20.3 vs. 41.8±23.3 ng/mL·6 h) were not different between conditions (p≥0.25). Cardiometabolic outcomes (plasma glucose/triacylglycerol, heart rate, blood pressure), liver function (plasma alanine aminotransferase/aspartate aminotransferase), kidney function (plasma creatinine), and subjective feelings/symptoms were not different between conditions (p≥0.07). Conclusions: Plasma CBD profiles were comparable between CBD-Caps and CBD-Drops, suggesting that there were not meaningful differences in routes of CBD absorption between conditions. This implies that CBD oil delivered sublingually is swallowed before oral mucosal CBD absorption occurs, which may have implications for research design, CBD product design, and consumer product choice.

Formulation and Evaluation of Pulsatile Drug Delivery System of Dexlansoprazole

Background: A pulsatile drug delivery system is intended to deliver drugs according to the circadian rhythm, or disease cycle. PDDS prepared by pulsincap technology contain a cross-linked hard gelatin capsule filled with the optimized immediate-release tablet, sodium alginate beads. Dexlansoprazole is used to treat the signs and symptoms of gastroesophageal reflux disease (GERD), erosive esophagitis, and stomach ulcers. Objective: The objective of the research is to develop and analyse a controlled-release pulsatile medication delivery system for the treatment of peptic ulcers that contains dexlansoprazole. Method: The Pulsincap system consists of a hard gelatin capsule containing an immediate-release tablet prepared by direct compression, sodium alginate beads prepared by the ionotropic gelatin method, and a hydrogel plug made through direct compression. The hydrogel plug was prepared by using various grades of HPMC polymer. The immediate-release tablet was prepared by direct compression. Result: The results of the present FTIR studies concluded that there was no interaction between dexlansoprazole and the excipient. Based on the evaluation parameter, it was found that the F2 tablet (1:2) ratio and 2% sodium alginate beads showed better results. Polymer HPMC K15M for Hydrogel showed the desired swelling time. Conclusion: It was concluded that the preparation of a pulsatile drug delivery system for dexlansoprazole through pulsincap technology can give drug release in a pulsed manner that is first immediate release, lag time, and sustain action.

Effect of the Encapsulation Process on the Viability of Probiotics in a Simulated Gastrointestinal Tract Model Medium

The primary objective of this study was to investigate the survival rate of three species of encapsulated bacteria (Propionibacterium acidipropionicici, Propionibacterium freudenreichii, and Propionibacterium thoenii) in model solutions designed to simulate the acidity levels found within the human gastrointestinal tract. The capsules were prepared by extrusion from gelatin and sodium alginate in a 1:1 ratio on a laboratory encapsulator. The use of gelatin and sodium alginate was found to provide optimum characteristics suitable for encapsulation of live bacteria. Three strains of Propionibacterium asidirgorionici, Propionibacterium freudenreichii, and Propionibacterium thoenii were subjected to in vitro assay to evaluate their probiotic potential. The final cell survival rate of P. freudenreichii was 105 CFU/mL, indicating that this probiotic is sensitive to acidic medium. The viability of encapsulated probiotics was studied in a model medium simulating the gastrointestinal tract. It was found that alginate–gelatin capsules could provide protection to P. freudenreichii from gastric acid and lead to high levels of viable bacteria released in the intestine. Practical application: Encapsulation of Propionibacterium freudenreichii into alginate–gelatin capsules produced capsules capable of delivering live probiotic bacteria into the intestine.

Simultaneous determination of paracetamol and caffeine by RP-HPLC in soft gelatin capsules

A rapid and stability-indicating RP-HPLC method was developed for simultaneous estimation of paracetamol and caffeine in soft gelatin capsules form especially to get some more advantages over other methods already developed for this combination. The method was validated according to ICH guideline with respect to accuracy, precision, specificity, linearity, solution stability, robustness, sensitivity, forced degradation and system suitability. For this, an isocratic condition of mobile phase comprising acetonitrile and phosphate buffer (pH 3.5) in a ratio of 15:85, v/v over YMC C18 column (250 × 4.6 mm, 5 μm) at a flow rate of 1 mL/minute at ambient temperature was maintained. The method showed excellent linear response with correlation coefficient (R2) values of 0.999 and 1.0 for paracetamol and caffeine respectively, which were within the limit of correlation coefficient (R2 > 0.995). The percent recoveries for two drugs were found within the acceptance limit of (98.0–102.0%). % RSD values for repeatability, reproducibility and Intermediate precisions were below 2.0. Forced degradation of the drug product was carried to establishing the stability-indicating property of this method and providing useful information about the degradation pathways, degradation products, and how the quality of a drug substance and drug product changes with time under the influence of various stressing conditions.

Acute Effects of Single Versus Combined Inhaled β2-Agonists Salbutamol and Formoterol on Time Trial Performance, Lung Function, Metabolic and Endocrine Variables

BackgroundHigh prevalence rates of β2-agonist use among athletes in competitive sports makes it tempting to speculate that illegitimate use of β2-agonists boosts performance. However, data regarding the potential performance-enhancing effects of inhaled β2-agonists and its underlying molecular basis are scarce.MethodsIn total, 24 competitive endurance athletes (12f/12m) participated in a clinical double-blinded balanced four-way block cross-over trial to investigate single versus combined effects of β2-agonists salbutamol (SAL) and formoterol (FOR), to evaluate the potential performance enhancement of SAL (1200 µg, Cyclocaps, Pb Pharma GmbH), FOR (36 µg, Sandoz, HEXAL AG) and SAL + FOR (1200 µg + 36 µg) compared to placebo (PLA, Gelatine capsules containing lactose monohydrate, Pharmacy of the University Hospital Ulm). Measurements included skeletal muscle gene and protein expression, endocrine regulation, urinary/serum β2-agonist concentrations, cardiac markers, cardiopulmonary and lung function testing and the 10-min time trial (TT) performance on a bicycle ergometer as outcome variables. Blood and urine samples were collected pre-, post-, 3 h post- and 24 h post-TT.ResultsMean power output during TT was not different between study arms. Treatment effects regarding lung function (p < 0.001), echocardiographic (left ventricular end-systolic volume p = 0.037; endocardial global longitudinal strain p < 0.001) and metabolic variables (e.g. NR4A2 and ATF3 pathway) were observed without any influence on performance. In female athletes, total serum β2-agonist concentrations for SAL and FOR were higher. Microarray muscle gene analysis showed a treatment effect for target genes in energy metabolism with strongest effect by SAL + FOR (NR4A2; p = 0.001). Of endocrine variables, follicle-stimulating hormone (3 h Post–Post-TT), luteinizing hormone (3 h Post–Pre-TT) and insulin (Post–Pre-TT) concentrations showed a treatment effect (all p < 0.05).ConclusionsNo endurance performance-enhancing effect for SAL, FOR or SAL + FOR within the permitted dosages compared to PLA was found despite an acute effect on lung and cardiac function as well as endocrine and metabolic variables in healthy participants. The impact of combined β2-agonists on performance and sex-specific thresholds on the molecular and cardiac level and their potential long-term performance enhancing or health effects have still to be determined.Trial registration: Registered at Eudra CT with the number: 2015-005598-19 (09.12.2015) and DRKS with number DRKS00010574 (16.11.2021, retrospectively registered).

Capsulated Cellular Nanosponges for the Treatment of Experimental Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD) is a chronic gastrointestinal tract disorder characterized by uncontrolled inflammatory responses to the disrupted intestinal epithelial barrier and gut microbiome dysbiosis. Currently available small-molecule immunosuppressive agents and anticytokine biologics show limited potency, mainly due to the complexity of the inflammatory network involved in IBD. Here, we develop an oral formulation of macrophage membrane-coated nanoparticles capsulated in enteric polymer-coated gelatin capsules (denoted "cp-MΦ-NPs") for IBD treatment. The capsules protect the nanoparticles from gastric degradation and allow for targeted delivery to the colon. At the inflamed colon, cp-MΦ-NPs act as macrophage decoys that bind and neutralize pro-inflammatory cytokines. The in vivo treatment efficacy of cp-MΦ-NPs is tested in a mouse model of dextran sulfate sodium-induced colitis. In both prophylactic and delayed treatment regimens, the oral delivery of cp-MΦ-NPs significantly alleviates IBD severity, reflected by reduced intestinal inflammation and intestinal barrier restoration. Overall, cp-MΦ-NPs provide a biomimetic nanomedicine strategy for the treatment of IBD.

Evaluating the Rumen Degradation of Novel Protected Gelatin Capsules Containing Fish Oil Fed to Lactating Dairy Cows.

The objective of this study was to assess the effects of feeding gelatin capsules containing fish oil, treated with alcoholic solutions of flavoring agents followed by drying, on lactation performance, rumen fatty acids content and milk enrichment of fatty acids. In Trial 1, four multiparous ruminally fistulated Holstein cows were randomly assigned to one of four dietary treatments sequences in a 4 × 4 Latin square design. Treatments consisted of (1) Control with no capsules, (2) Control plus 200 untreated capsules per cow/day, mixed with the TMR, (3) Control plus 200 treated capsules per cow/day placed directly into the rumen, (4) Control plus 200 treated capsules per cow/day, mixed with the TMR. In Trial 2, three fistulated Holstein and three fistulated Jersey multiparous cows were randomly assigned to three dietary treatments sequences in a replicated 3 × 3 Latin square design. Treatments consisted of (1) Control with no capsules fed to the cows, (2) Control plus 180 untreated capsules per cow/day, (3) Control plus 180 treated capsules per cow/day. Compared to control, feeding fish oil capsules significantly (Trial 1) or numerically (Trial 2) reduced milk fat concentration and yield. Furthermore, in both trials, the feeding of untreated or treated capsules had no effect on animal performance or milk composition. In both trials, compared to controls, supplementing the diet with fish oil capsules consistently increased total trans C18:1 isomers and DHA concentration in the rumen and milk fat. However, for both trials, capsule protection treatment had a minimal effect on the concentration of any of the reported rumen and milk fatty acids. When assessed under laboratory control conditions, due to water absorption, the treated capsule weight was increased by 40% while resistance to pressure decreased by 84% after 2 h of incubation in water. The results of this study suggest that due to a reduction in the capsule shell's resistance to abrasion, treated capsules marginally prevented the release of fish oil in the rumen.