Capsule Formulation Research Articles

STABILITY-INDICATING RP-HPLC METHOD DEVELOPMENT AND VALIDATION FOR THE ANALYSIS OF DOXEPIN HYDROCHLORIDE IN BULK AND PHARMACEUTICAL DOSAGE FORM

Objective: A simple, reliable, and rapid RP-HPLC method showing stability has been established to detect Doxepin Hydrochloride (DOX) with its degraded products. The proposed method has been validated for specificity, linearity, system suitability, accuracy, precision, robustness, LOD, and LOQ as per ICH guidelines. All parameters were found to be within the accepted limits, affirming the method's reliability. Methods: Analysis was conducted using RP-HPLC on a Phenomenex C18 Luna column (250 mm × 4.6 mm id, 5 µm) with a mobile phase comprising methanol, acetonitrile, and buffer (40:30:30, v/v/v) and a flow rate of 0.5 ml/min. The detection was performed with a UV detector set at 254 nm. Diverse methods have been employed to investigate forced degradation studies, including acid-base hydrolysis, photolysis, thermal degradation, and oxidation. These studies were conducted both in bulk and in capsule formulations of DOX. Results: The retention time (tR) of DOX was 2.92 minutes, and all parameters met acceptable limit values. The response exhibited linearity over a concentration range of 10 to 50 µg/ml (R2 = 0.9974). The percentage of DOX recovered from the pharmaceutical cream dosage form ranged from 97.67% to 101%. Sensitivity levels for the developed method were indicated by limit of detection (LOD) and limit of quantification (LOQ) values of 0.40–0.50 µg/ml. The proposed method was validated according to ICH guidelines. Conclusion: Hence, a simple, reliable, accurate, and precise HPLC method was developed, proving suitable for the analysis of DOX in both bulk and commercial formulations.

The Effect of Drying Time on the Antioxidant Properties of Single Black Garlic Powder

Black garlic is a processed product derived from fresh garlic that generally has a taste and aroma that is less preferred. A drying process is employed to increase the attractiveness of consuming black garlic. This study aims to assess the impact of the drying time on the antioxidant activity and content of antioxidant compounds such as phenolics, flavonoids, and tannins in single black garlic. The drying time is expected to yield a single black garlic powder that is more convenient for consumption, whether in capsule form or as an addition to food products. With low moisture content, single black garlic powder has a longer shelf life and high antioxidant activity, potentially commanding a higher market value. In this research, the drying time was carried out on a single black garlic using an oven for 6, 12, 18, and 24 hours. The analysis of the total phenolic content (TPC), entire tannin content (TTC), and total flavonoid content (TFC) was determined using a Uv-Vis spectrophotometer, and each component was measured concerning gallic acid equivalent for TPC, quercetin for TFC, and tannic acid for TTC. Antioxidant activity was determined using the DPPH method, and the outcomes were expressed as IC50 values. The research shows that the extended drying time leads to an augmentation of the antioxidant compound in black garlic. Drying for 24 hours produces significant outcomes, showing potent antioxidant activity with an IC50 value of 37,019 ppm (powerful antioxidant category), total phenolic content value is 44,785 ± 0,033 mgGAE/g, total flavonoid content value is 32,033 ± 0,008 mgQE/g, and total tannins content value is 74,884 ± 0,057 mgTAE/g. Statistical analysis using a one-way ANOVA showed a significant influence of drying time on TPC, TFC, and TTC (p < 0,05). The longer the drying time, the higher the antioxidant activity and the content of compounds acting as antioxidants in black garlic powder.

Effect of Bergenia ligulata (Wall.) in type 2 diabetes mellitus: A randomized placebo-controlled trial

IntroductionGlobally 8.8 % of people aged 20–79 years have diabetes. Diabetes mellitus (DM) is a group of metabolic disorders characterized by hyperglycemia. Bergenia ligulata (Wall.) is a small, perennial, rhizomatous flowering herb used medicinally in India.The present study aimed to evaluate the effect of B. ligulata rhizome as an adjuvant in decreasing blood glucose levels in type-II diabetes mellitus. MethodsForty patients were enrolled in a single-blind, randomized, placebo-controlled study; twenty patients were assigned to each of the test and control groups. Only those currently using 2 or less oral hypoglycaemic agents were included. Subjects took B. ligulata (4 gm) or placebo in capsule form, orally, for 8 weeks. Fasting blood sugar (FBS) and postprandial blood sugar (PPBS) were measured at baseline, fourth week, and end of the trial. Haemoglobin A1c (HbA1c) and quality of life (Asian Diabetes Quality of Life; ADQOL) scores were measured at baseline and the end of the trial. Data were statistically analyzed using analysis of variance (ANOVA), student's t-test, chi-square, and Fisher exact test to assess the effect of the intervention. ResultsAfter 8 weeks of treatment, the decrease in mean fasting blood sugar (FBS) level showed a significant difference between groups (Cohen's d= -0.457, 95 % confidence intervals (CIs) -0.174 to -1.082). PPBS level was significantly reduced in the test group compared to the control group (Cohen's d= -1.457, 95 % confidence interval (CIs) -0.749 to -2.150). There was a statistically significant reduction in HbA1c level in the test group compared to the control group (Cohen's d= -0.798, 95 % confidence interval (CIs) -0.148 to -1.438). B. ligulata was found to be more effective in improving ADQOL scores than placebo (Cohen's d = 0.762, 95 % confidence interval (CIs) 0.115 to 1.400). No B. ligulata related adverse events were observed. ConclusionB. ligulata appears to be an effective adjuvant treatment for type 2 diabetes mellitus. It reduced FBS, PPBS, and HbA1c and improved ADQOL scores significantly compared to the placebo. However, for more valid results, larger samples are needed. Clinical trial registration noCTRI /2019/05/019087.

Serdexmethylphenidate/dexmethylphenidate capsules for children and adolescents with attention-deficit/hyperactivity disorder (ADHD): a plain language summary

What is this summary about? This is a plain language summary of 2 articles published in the Journal of Child and Adolescent Psychopharmacology. It describes a medication called serdexmethylphenidate/dexmethylphenidate, or SDX/d-MPH for short. SDX/d-MPH is marketed under the name Azstarys®. It is in capsule form taken by mouth once a day in the morning and meant for treating patients aged 6 years and older with attention-deficit/hyperactivity disorder, commonly referred to as ADHD. This summary focuses on studies that were done in children and adolescents aged 6 to 12 years with ADHD. The study results showed how SDX/d-MPH reduced the symptoms of ADHD, how fast the medication began to work and for how long it worked in the study patients, as well as the medication's safety during 1 year of treatment. What are the key takeaways? Two main studies were done in patients with ADHD. The first study was conducted in a laboratory classroom, which is a simulated school classroom setting with children and adolescents aged 6 to 12 years with ADHD. The patients received either SDX/d-MPH or a placebo. The results of this study showed that the effect of SDX/d-MPH on reducing ADHD symptoms started approximately 30 minutes after taking the SDX/d-MPH capsule and lasted for approximately 13 hours. The placebo did not have this effect. The most common side effects for those taking SDX/d-MPH were headache, abdominal (belly) pain, insomnia and upper respiratory tract infection. The second study was also done in patients aged 6 to 12 years with ADHD. The purpose was to examine how safe and tolerable SDX/d-MPH was during 1 year of treatment. In this study, no placebo was given. The findings from the second study showed that SDX/d-MPH was safe and tolerable during the 1-year treatment period, with the most common side effects being decreased appetite, upper respiratory tract Scott H. Kollins1,2, Andrea Marraffino3, Andrew J. Cutler4,5, Charles Oh6, Matthew N. Brams7, Rene Braeckman8 & Ann C. Childress9 1 Duke University School of Medicine, Durham, NC, USA; 2 Akili Interactive, Inc., Boston, MA, USA; 3 Accel Research Sites Network, Maitland, FL, USA; 4 SUNY Upstate Medical University, Syracuse, NY, USA; 5 Neuroscience Education Institute, Lakewood Ranch, FL, USA; 6 Corium LLC, Boston, MA, USA; 7 Bayou City Research, Houston, TX, USA; 8 Zevra Therapeutics Inc, Celebration, FL, USA; 9Center for Psychiatry and Behavioral Medicine, Las Vegas, NV, USA Placebo: an inactive substance that has no medication but looks exactly the same as the actual medication and is taken in exactly the same way as the study drug. Side effect: an undesirable effect of a medication. Insomnia: difficulty sleeping. Tolerable: means that a patient can endure a medication even with the some of the side effects. infection, sore throat and nose, decreased weight and irritability. This study also showed that SDX/d-MPH was effective throughout the 1-year treatment period. What were the main conclusions? In the first study, children with ADHD treated with SDX/d-MPH showed noticeable improvements in ADHD symptoms as early as 30 minutes after the medication was given, and those improvements lasted up to 13 hours. SDX/d-MPH was also found to be as safe as other ADHD treatments containing methylphenidate (MPH). Results of the second study showed that children with ADHD could be treated safely with SDX/d-MPH. Clinical Trial Registration: NCT03460652 ( ClinicalTrials.gov )

Development and Validation of a New Reversed Phase HPLC Method for the Quantitation of Azithromycin and Rifampicin in a Capsule Formulation.

This research aimed to develop a new method for simultaneously estimating the presence of azithromycin (AZT) and rifampicin (RIF) in a capsule formulation using reverse-phase high-performance liquid chromatography. The developed method utilized a Gemini column with a 60:40% v/v acetonitrile and potassium dihydrogen phosphate mobile phase, a flow rate of 1mL/min, and an injection volume of 20μL. The detection wavelengths of 210 and 254nm for AZT and RIF, respectively, were used. Validation ensures specificity with a peak purity index > 0.99999 for AZT and >0.99995 for RIF, affirming unambiguous analyte detection. The system suitability test, within acceptable limits, validates method reliability. Linearity calibration curves (R2 = 0.998) cover a 25-150% target concentration range. Accuracy studies employing the standard addition method yield recovery values between 96.6 and 103.9% for both drugs, confirming method accuracy. Precision studies reveal % relative standard deviation values consistently below 2%, highlighting reproducibility. Robustness testing supports method reliability under varying conditions. Application to a pharmaceutical capsule formulation demonstrates the method's practicality, accurately quantifying AZT (98.30%) and RIF (99.37%). This study provides a validated analytical approach for simultaneous quantification in commercial pharmaceutical products containing both drugs, enhancing pharmaceutical quality control for critical antibiotics in complex formulations.

A PROSPECTIVE COMPARATIVE STUDY ON EFFICACY OF ORAL VITAMIN D FORMULATIONS IN PATIENTS WITH CHRONIC LOW BACK PAIN WITH VITAMIN D DEFICIENCY AT A TERTIARY CARE HOSPITAL

Objective: Chronic low back pain is a global health problem with significant medical and economic burden. Vitamin D deficiency and obesity are its risk factors. The objective was to determine efficacy of oral vitamin D formulations in patients with chronic low back pain with vitamin D deficiency.
 Methods: A prospective analytical cohort study was conducted. Patients with self-reported chronic low back pain and with vitamin D concentrations ≤30 ng/dl were identified and randomized into 3 groups namely Granule, Nano syrup and soft gel capsule group. Vitamin D supplementation of 60,000 IUs per dose for ten consecutive days was given in the form of granule (1 g sachet), Nano syrup (5 ml bottle) and soft gel capsule. We measured (25-hydroxyvitamin D [25(OH)D]) concentrations and to assess pain, Visual analogue scale and Modified Oswestry low back pain disability questionnaire (MODQ) were used before and 12 w after the intervention.
 Results: After 12 w 25(OH)D levels increased significantly with vitamin D supplementation in all the groups but more in the Nano syrup group. There was also significant reduction in back pain intensity in all the groups after vitamin D supplementation. However in Nano syrup group, there was a significantly greater reduction in back pain compared with other groups.
 Conclusion: Our findings suggest that vitamin D supplementation in vitamin D deficient adults may improve chronic low back pain. Hence, testing for vitamin D deficiency in those with chronic low back pain may be warranted.

Coenzyme Q10: A Key Antioxidant in the Management of Diabetes-Induced Cardiovascular Complications-An Overview of Mechanisms and Clinical Evidence.

Diabetes mellitus (DM) presents a significant global health challenge with considerable cardiovascular implications. Coenzyme Q10 (CoQ10) has gained recognition for its potential as a natural antioxidant supplement in the management of diabetes and its associated cardiovascular complications. This comprehensive review systematically examines the scientific rationale underlying the therapeutic properties of CoQ10 in mitigating the impact of diabetes and its cardiovascular consequences. The analysis encompasses preclinical trials (in vitro and in vivo) and clinical studies evaluating the efficacy and mechanisms of action of CoQ10. Result & Discussion. Findings reveal that CoQ10, through its potent antioxidant and anti-inflammatory attributes, demonstrates significant potential in reducing oxidative stress, ameliorating lipid profiles, and regulating blood pressure, which are crucial aspects in managing diabetes-induced cardiovascular complications. CoQ10, chemically represented as C59H90O4, was administered in capsule form for human studies at doses of 50, 100, 150, 200, and 300 mg per day and at concentrations of 10 and 20 μM in sterile powder for experimental investigations and 10 mg/kg in powder for mouse studies, according to the published research. Clinical trials corroborate these preclinical findings, demonstrating improved glycemic control, lipid profiles, and blood pressure in patients supplemented with CoQ10. In conclusion, CoQ10 emerges as a promising natural therapeutic intervention for the comprehensive management of diabetes and its associated cardiovascular complications. Its multifaceted impacts on the Nrf2/Keap1/ARE pathway, oxidative stress, and metabolic regulation highlight its potential as an adjunct in the treatment of diabetes and related cardiovascular disorders. However, further extensive clinical investigations are necessary to fully establish its therapeutic potential and assess potential synergistic effects with other compounds.

Formulation of category-2 hypoglycemic Improved Traditional Medicines from selected Cameroonian medicinal plants: <i>Mangifera indica, Persea americana</i> and <i>Ageratum conyzoides</i>

Diabetes mellitus is the fourth leading cause of death worldwide, and constitutes a major public health crisis. Management of the adverse condition relies mostly on synthetic drugs such as metformin, glibenclamide and insulin. However, treatment with synthetic drugs is challenged by side effects and high cost especially to patients in low-income countries like Cameroon. This study set out to formulate Improved Traditional Medicines (ITMs) in the form of capsules from lyophilized aqueous leaf extracts of Ageratum conyzoides, Mangifera indica and Persea americana, in combination, coded as ITM-1, and leaf extract of Mangifera indica alone, referred to as ITM-2. Phytochemical profiling of individual extracts was carried out using standard methods, while their antioxidant activity was evaluated in vitro by the 2,2-diphenyl-1-picryhadrazyl reducing (DPPH) assay and the Ferric (Iron) reducing antioxidant power assay (FRAP). Capsule formulation was guided by findings from prior Physicochemical and pharmacotechnical analysis of individual extracts and their combination. Safety studies were carried out both in vitro (cytotoxicity testing in Vero cells); and in vivo (acute toxicity tests using the mouse model). Preliminary evaluation of the antidiabetic potential of the formulated ITMs was achieved through determination of their acute hypoglycemic and antihyperglycemic properties in Wistar rats (Oral Glucose Tolerance Test). Major classes of phytochemicals detected were alkaloids, phenols, tannins, flavonoids, anthocyanins, tri-terpenes and anthraquinones. The DPPH and FRAP assays showed dose-dependent antioxidant activity for ITM-1 and ITM-2. Both ITMs showed no toxic effects, be it in vitro, (Cytotoxic Concentration 50% - CC50>1000 µg/mL in cells) or in vivo. At the dose of 25 mg/Kg, both ITMs exhibited significant hypoglycemic effects in Wistar rats. The ITM-2 capsules completely suppressed post-prandial glucose peak in rats as compared to the negative control (distilled water), ITM-1 capsule was able to cause restoration of the glucose levels to normal levels after 120 minutes

Evaluation of Antihyperlipidaemic and Cardioprotective Action of a Herbal Formulation

As per WHO, Cardiovascular diseases (CVDs) are the leading cause of death globally. CVDs also impart a huge financial burden and remain a hurdle for sustainable development in low and middle income countries. Hence there is an urgent need to identify individuals with high CVD risk and begin appropriate preventive intervention well in advance. In this study, 60 individuals of either sex, within the age group of 30 – 70 years, having hyperlipidaemia along with more than 10% of CVD risk were identified in lipid screening camps with the help of JBS 3 Heart Risk android application tool. A combination of three well known herbs in capsule form containing 500mg extract of Guggulu (Commiphora mukul), Pushkarmool (Inula racemosa) and Arjuna (Terminalia arjuna) in equal proportion was administered in a dose of 1 capsule twice daily after food with warm water for 3 months to treat hyperlipidaemia. Only 55 participants completed the trial. Different parameters of lipid profile, CVD risk score and biological heart age were compared before and after treatment using appropriate statistical method. The intervention resulted in reduction of total cholesterol by 17.49%, LDL by 21.04%, VLDL by 24.55% and Triglycerides by 24.55% whereas HDL increased by 10.48 %. As a secondary outcome, the mean CVD risk score was reduced by 6.91% and the mean biological heart age was also reduced by 6.64 years. The trial drug was well tolerated and free from adverse effects. Hence the trial drug can offer a safe and effective solution to individuals with hyperlipidaemia and moderate CVD risk.

Salivary Cortisol Measurement Contamination After Oral Hydrocortisone: A Randomized Crossover Trial.

The study aimed to evaluate salivary cortisol (SC) contamination and determine the associated factors in secondary adrenal insufficiency (SAI) patients treated with hydrocortisone (Hc). A randomized crossover trial involved SAI patients. SC was measured before the morning Hc dose, then at one, two, and four hours after. The procedure was performed twice on two days of a week: one day while taking Hc in tablet form (tablet set) and one day while taking Hc in capsule form (capsule set). Area under the curve (AUC) of SC levels over time was calculated in each participant for the two sets. SC contamination was defined as AUCtablet above the 95th percentile of AUCcapsule. Thirty-four patients (24 females and 10 males) with a median age of 48 years were enrolled. Post-Hc dose SC levels were higher in tablet than in capsule set, particularly at one hour. Prevalence and extent of SC contamination were estimated to 32% and 88%, respectively. In capsule set, SC measured two hours after Hc intake showed the strongest correlation with AUC (r=0.88, p<0.001). In multivariate analysis, serum potassium≥3.9 mEq/l was the only predictor for SC contamination [multi-adjusted OR (95% CI): 7.1 (1.4-36.1); p=0.018]. SC measured during the two hours after Hc intake is inaccurate for glucocorticoid replacement therapy assessment in SAI patients treated with Hc in tablet form.

Psoariasis Vrs Alstonia Scholaris: Computational Validation as Functional Food

Introduction : Psoriasis is a skin disease. It is rare &amp; is expanding worldwide. In this investigation the ion channel protein TRPV3 (Transient receptor potential cation channel, subfamily III ) has been targeted vis-à-vis psoriasis, which is a important factor.&#x0D; Objective : To find out Alstonia scholaris’s phyto compounds efficacy against psoriasis and use as functional food.&#x0D; Material and Methods : (i) The sun dried powder of the whole bark of medicinal plant Alstonia scholaris in capsule form @450mg/cap as ‘Functional Food’ in Fixed dose (ii) Two phytocompounds (Alstolenine and (-) Scholarine) were taken from the mature tree’s bark for In Silico investigation.&#x0D; Results : (i) Functional Food use as was administered and results recorded indicate near clear results with no toxicity. In-Silico molecular docking indicates Alstolenine as the champion with a binding affinity of -7.25 kcal/mol against the TRPV3 ion channel. It is also non-toxic. Synergistic with conventional therapeutics : vis-à-vis psoriasis.&#x0D; Conclusion : Alstonia scholaris bark as whole supports use as ‘Functional Food’. Alstolenine posits as a good candidate for further ‘Drug Discovery’ related studies : vis-à-vis psoriasis.

The hidden dangers lurking at home: Unveiling the prevalence of leftover antibiotics and its associated factors among Lebanese households

BackgroundAntimicrobial Resistance (AMR) is a major global concern. Irrational use of antibiotics including self-medication (SM) with leftovers without a medical prescription can be a leading cause. This study aimed to investigate the prevalence and related factors of leftover antibiotics (LA) in Lebanese households. Study designA cross-sectional study of the Lebanese population was conducted between March and October 2022. MethodsThrough random proportional stratified sampling, a total of 494 families participated in this study. Data collection was carried out through phone calls using a comprehensive and reviewed questionnaire. The data was then analyzed using SPSS version 26. Logistic regression was utilized to identify the factors associated with LA, with the presence of LA in households as the dependent variable and other factors such as age, region of residence, and presence of elderly individuals at home as the independent variables. ResultsAmong selected households, 118 households (23.89%) had LA. The most common type of antibiotic found was penicillin (59.84%). Most of the LA were in the form of tablets and capsules (94%) with valid expiration dates (87%). Antibiotics were mainly prescribed by doctors (61%), and the main reason for prescribing was acute respiratory tract infections (47.46%). SM was reported by 42.37% of the families with LA. A family with elderly patients (p = 0.002; OR = 2.23; 95% CI = 1.33–3.73) and those residing in Mount Lebanon (p = 0.019; OR = 2.28; 95% CI = 1.14–4.56) had significantly higher odds of having LA. ConclusionLeftover antibiotics were found in nearly a quarter of the addressed Lebanese families. Therefore, public educational campaigns should be launched to limit injudicious antibiotic use including SM, and to promote proper disposal of any leftovers. It is also crucial to adopt the One Health approach by developing national programs for the safe disposal of LA and implementing regulations to restrict the distribution of antibiotics in pharmacies without a prescription.

Intranasal Drug Delivery of Antiviral Agents - A Revisit and Way Forward

Abstract: Even to this date, oral drug delivery in the form of tablets, capsules, and syrups is considered as the most accepted one. However, oral delivery as a methodology requires that the active molecules and their formulations are water-soluble. Nasal drug delivery is characterized by ease of permeability through the epithelial mucosa, low enzyme activity, and a wide range of immunocompetent cells. For the transfer of drugs and active molecules through the nasal route, it is often essential to resort to nanodelivery methods, such as liposomes, microspheres, nanoemulsions, and so on. The use of nanodelivery vehicles has become more important in the modern context of viral infections, including those of the respiratory tract. Nanoformulations are developed in the form of nasal gels, sprays, drops, rinses, etc. Nanoformulations of antigens, vaccine and immune adjuvants, and antivirals are now gaining importance. There are promising reports on nanoparticles of metals, metal oxides, polymers, and so on that have the potential to detect and inhibit viruses by themselves. This review looks into the nasal nanoformulations in detail and provides an insight into how their efficacy can be improved. To overcome known drawbacks, such as degradation and active mucociliary clearance by antigenpresenting cells at the site of administration, polymers, such as PEG, are incorporated in the nanoformulation. Polymeric systems also provide better tunability of physicochemical properties. The mechanism of nasal spray-based drug delivery systems is also discussed in this paper. The review, thus, provides a detailed insight into the way forward for the development of nasal formulations.

Influence of dietary supplementation with Lepidium meyenii (Maca) on sperm quality in dogs.

Maca is a traditional Andean crop used as a nutraceutical for the fertility-enhancing properties that are linked with antioxidant activity. The aim of this study was to evaluate, for the first time, the potential beneficial effects of oral Maca (Lepidium meyenii or Lepidium peruvianum) supplementation in improving reproductive performance in male dogs. Forty-eight male dogs of different breeds were enrolled in the study, fed the same maintenance diet, and exposed to the same environmental conditions. The subjects were divided into four groups of 12 dogs each: Subfertile treatment group, Subfertile control group, Normofertile treatment group, and Normofertile control group. The dogs in the treatment groups received Lepidium meyenii in their diet in a capsule formulation [75 mg/kg Maca extract 10:1, thickening agent (hydroxypropyl methylcellulose), ground rice], while the control groups received placebo capsule (starch). For each subject included in the study, the spermiogram was analyzed at three time points of the sperm cycle: at day 0 (T0), day 31 (T31), and day 62 (T62). Dietary supplementation with Maca in subfertile subjects resulted in a significant increase in ejaculate volume and total sperm count compared to the control group. This increase was also observed in normofertile subjects in the treatment group. In addition, total and progressive motility as well as sperm morphology were significantly improved in the groups treated with Maca compared to the control groups. The results thus highlight, for the first time, the potential efficacy of supplementation with 75 mg/kg of Maca extract daily in improving semen quality in dogs.

Ethnobotany, chemistry and toxicity of Petivera alliacea: A review

Petivera alliacea (Family, Phytolaccaceae) is a wild and perennial shrub used in traditional medicine, especially as an antirheumatic, analgesic, and for various respiratory diseases. There is little comprehensive data on P. alliacea's pharmacological, nutritional, and ethnobotanical characteristics, and it is not in a well-documented form. In the present review, efforts have been made to gather its detailed medicinal uses, chemical composition, and pharmacological properties. The goal of this review is to present an updated summary of documents sourced from recent publications regarding the ethnobotanical importance, pharmacology, toxicological properties, and phytochemistry of P. alliacea to further investigate this plant and learn about its potential impact on pharmaceuticals. This literature review used web-based systematic research. PubMed, Google Scholar, Mendeley, and CriticalReview were used to find studies reporting pharmacological, nutritional, and pharmacological properties. The ethnobotanical uses of P. alliacea include the treatment of respiratory disorders, fever, venereal diseases, and influenza. The nutritional uses include the use of the powder as herbal concoctions in the form of extracts, teas, and capsules intentionally for boosting immune systems. The reported pharmacological activities are antimicrobial, anti-inflammatory, antidiabetic, anticancer, immunostimulating and antinociceptive activities. Along with flavonoids, steroids, and triterpenes, P. alliacea also has sulfur-containing compounds like sulfides, polysulfides, and sulfoxides that make it unique. This review provides detailed information about the history, traditional importance, phytochemistry, and clinical impacts of the studied plant as food and medicine. Keywords: Petiveria alliacea, Traditional medicine, Pharmacological activities, Nutritional importance, Secondary metabolites

Creating a Framework for Treating Autoimmune Gastritis-The Case for Replacing Lost Acid.

Autoimmune gastritis (AIG) is characterized by the destruction of gastric parietal cells, resulting in hypochlorhydria and eventual achlorhydria, as oxyntic glands in the corpus are destroyed and become atrophic. The permanent loss of gastric acid has many impacts-both theoretical and documented. The most concerning of these are hypergastrinemia and increased N-nitroso compounds, both of which increase the risk of gastric cancers. While known deficiencies of B12 and iron are often replaced in AIG, acid is not. Moreover, patients with AIG are often prescribed acid suppression for a stomach that is decidedly no longer acidic, worsening the sequelae of gastric atrophy. Betaine hydrochloride (BHCL) is a short-acting acidifying agent, available over the counter in capsule form. Mealtime acid supplementation has an historic basis and could ameliorate many AIG-related gastrointestinal symptoms. Theoretically, acidification could also reduce the potential for hypergastrinemia and the production of N-nitroso compounds, consequently reducing the risk of gastric cancers. Supplemental vitamin C may also help in preventing gastric N-nitroso formation, regardless of the gastric pH. This narrative review describes the functions of gastric acid in gastrointestinal and immune health, documents the effects of hypochlorhydria in AIG, and proposes potential options for safely re-establishing the acid milieu of the stomach for patients with AIG.

A Concise Overview on Orodispersible Film along with their Formulation and Characterization Technique’s

Orally fast-dissolving medicine delivery techniques are increasingly common at present. Due to the desire for these delivery systems, oro-dispersible film (ODF) was recently introduced for the delivery of medicines via the oral route. Most of drugs are delivering through oral route in the form of tablets, capsules and liquids, because they are simple to make and have a greater level of patient compliance. But these conventional dosage forms have many problems including big size of dosage form, and fear of chocking. Oral rapid disintegrating/oro-dispersible drug delivery systems were created to tackle such issues. Fast dissolving films were invented for the patients who have swallowing issues with conventional/traditional oral solid dosage forms. They also have a quick onset of effect, taking only a few seconds, because the drug is absorbed directly from the injection site to the systemic circulation, avoiding first-pass metabolism. In the preparation of films, polymers, surfactants, flavoring agents, coloring agents, sweetening agents, saliva stimulating agents, drug, and plasticizer are used. The drug incorporated in ODF should have pleasing taste, low molecular weight, high stability, and high aqueous solubility. Solvent and semisolid casting, hot melt extrusion, and rolling techniques are routinely used to prepare ODFs. Thickness, loss on drying, tensile strength, and elongation percentage are commonly assessed for evaluating ODFs, as well as their resistance to tearing, weight variation, folding endurance, pH, swelling property, transparency, disintegration, dissolution rate, and stability. The purpose of this review article is to provide a quick overview of ODF delivery systems.

Phase II study investigating the efficacy and safety of glesatinib (MGCD265) in patients with advanced NSCLC containing MET activating alterations

ObjectivesDysregulated signaling by mesenchymal epithelial transition factor (MET) and heightened AXL activation are implicated in the pathogenesis of non-small cell lung cancer (NSCLC). Glesatinib (MGCD265) is an investigational, oral inhibitor of MET and AXL. Materials and methodsThis open-label, Phase II study investigated glesatinib (free-base suspension [FBS] capsule 1050 mg BID or spray-dried dispersion [SDD] tablet 750 mg BID) in patients with advanced, previously treated NSCLC across four cohorts grouped according to presence of MET activating mutations or amplification in tumor or ctDNA. The primary endpoint was objective response rate (ORR). ResultsSixty-eight patients were enrolled: n = 28 and n = 8 with MET exon 14 skipping mutations in tumor tissue and ctDNA, respectively, and n = 20 and n = 12 with MET gene amplification in tumor tissue and ctDNA, respectively. Overall, ORR was 11.8 %, median progression-free survival was 4.0 months, and median overall survival was 7.0 months. Among patients with MET activating mutations, ORR was 10.7 % with tumor testing and 25.0 % with ctDNA testing. For MET amplification, responses were observed only in patients enrolled by tumor testing (ORR 15.0 %). Diarrhea (82.4 %), nausea (50.0 %), increased alanine aminotransferase (41.2 %), fatigue (38.2 %), and increased aspartate aminotransferase (36.8 %) were the most frequent adverse events assessed as related to study medication. Glesatinib exposure was similar with the SDD tablet and FBS capsule formulations. The study was terminated early by the sponsor due to modest clinical activity. ConclusionsGlesatinib had an acceptable safety profile in patients with advanced, pre-treated NSCLC with MET activating alterations. Modest clinical activity was observed, which likely reflects suboptimal drug bioavailability suggested by previously reported Phase I data, and pharmacodynamic findings of lower than anticipated increases in circulating soluble shed MET ectodomain (s-MET).

Therapeutic effects of probiotics and herbal medications on oxalate nephrolithiasis: a mini systematic review.

The majority of all kidney stone cases are oxalate urolithiasis with a high risk of recurrence. Beside its widespread occurrence, kidney stones are characterized by severe complications and high treatment costs. Probiotics and herbal medications could be forthcoming therapeutic interventions in the management of oxalate kidney stones. The PubMed/MEDLINE database was searched for keywords "Oxalobacter formigenes" AND "Oxalate" OR "oxalate degradation" AND "Lactobacillus" OR "Bifidobacterium" OR "recombinant Lactobacillus" OR "Bacillus subtilis", and "urolithiasis" AND "herbal extract". The search returned 253 results, 38 of which were included in the review. Most of the oxalate-degrading probiotics belong to the Oxalobacter formigenes, Lactobacillus, Bifidobacterium, and Bacillus genus with a minimum dosage of 107 CFU in the form of capsules, sachets, and lyophilized powder. Oxalate concentration in media was 5-50mM with an incubation time ranging from 24h to 14 days. The majority of the studies suggested that probiotic supplementation might be useful for reducing urinary excretion of oxalate and urea and alleviation of stone formation. Different herbal extracts were used on murine models of nephrolithiasis (induced by 0.5-3% ethylene glycol) with reduction of renal inflammation and urinary parameters, and calcium oxalate crystals. Several strains of probiotics and herbal extracts confer protective effects against kidney stone/nephrolithiasis, indicating their promising nature for being considered as elements of preventive / adjuvant therapeutic strategies.

Structural Elucidation of Novel Degradation Impurities of Ibrutinib in Ibrutinib Tablets Using Preparative Chromatography, LCMS, HRMS and 2D NMR Techniques

Abstract Ibrutinib is an orally administered compound that functions as an irreversible covalent inhibitor of the Bruton tyrosine kinase, an essential element in multiple cellular processes including B-cell differentiation, proliferation, migration, survival and apoptosis. The compound has been found to demonstrate efficacy against a range of B-cell malignancies. The drug product is available in oral tablet and capsule formulations. The drug degradation profiles of tablets dosage form were assessed in accordance with regulatory guidelines. The results indicate that the drug substance is susceptible to alkaline and oxidative stress. The oxidation degradation led to the identification of three significant unknown degradation impurities. The three compounds were isolated through the application of preparative liquid chromatography, and their structures were determined using analytical techniques such as liquid chromatography–mass spectrometry, high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. Utilizing structural elucidation data, predictions were made regarding the composition of impurities, revealing them to be novel degradation impurities that bear structural resemblance to ibrutinib. Additionally, potential pathways for the formation of the impurities were proposed.