Desenvolvimento de organogel injetável subcutâneo de Pluronic®-F127 e lecitina de soja (OPL) contendo meloxicam para uso veterinário / Development of a veterinary organogel formulation containing soy lecithin, Pluronic® F-127 and meloxicam for the treatment of acute and chronic pain in small animals

O organogel é formado por uma matriz tridimensional composta de filamentos que se auto-organizam em uma rede entrelaçada e que, por seu tipo de estrutura, pode ser utilizado com o objetivo de atuar como um implante que se forma in situ, sendo capaz de se comportar como uma forma farmacêutica de liberação prolongada. Esse trabalho tem, por tanto, o objetivo desse trabalho foi desenvolver, caracterizar, quantificar e traçar perfis de dissolução para formulações de organogel contendo meloxicam como principio ativo. O material está dividido em quatro capítulos, sendo apresentada inicialmente (I) revisão da literatura a respeito da lecitina de origem vegetal, com suas principais fontes de obtenção, como soja, girassol e colza, e também seu uso farmacêutico na obtenção de formulações como organogéis, microemulsões e lipossomas. Os demais capítulos abordam (II) desenvolvimento e otimização de uma formulação de organogel contendo lecitina de soja e Pluronic® F-127 como formadores da matriz tridimensional e meloxicam como principio ativo. (III) Desenvolvimento e validação de um método de quantificação do teor de meloxicam por cromatografia líquida de alta eficiência (CLAE). (IV) Desenvolvimento de um método de dissolução para formulações de organogel, que fosse capaz de ser utilizado na caracterização do perfil de dissolução de diferentes formulações. Com os resultados obtidos, foi possível desenvolver formulações de organogel contendo lecitina de soja, Pluronic® F-127 e meloxicam, assim como um método analítico validado para as analises de teor. Por fim, foram obtidos também os perfis de dissolução de duas formulações mais promissoras

Organogels are formed by a three-dimensional matrix composed of filaments that selforganize in an interlaced network and that, due to its type of structure, can be used with the objective of acting as an implant that forms in situ, being able to behave as an extendedrelease dosage form. This work has, therefore, the objective of this work was to develop, characterize, quantify and trace dissolution profiles for organogel formulations containing meloxicam as active ingredient. The material is divided into four chapters, initially presented (I) review of the literature on lecithin of plant origin, with its main sources of production, such as soybean, sunflower and rapeseed, and also its pharmaceutical use in obtaining formulations such as organogels , microemulsions and liposomes. The remaining chapters address (II) development and optimization of an organogel formulation containing soy lecithin and Pluronic® F-127 as three-dimensional matrix formers and meloxicam as an active ingredient. (III) Development and validation of a method for quantification of meloxicam content by high performance liquid chromatography (HPLC). (IV) Development of a dissolution method for organogel formulations, capable of being used to characterize the dissolution profile of different formulations. With the results obtained, it was possible to develop organogel formulations containing soy lecithin, Pluronic® F-127 and meloxicam, as well as a validated analytical method for content analysis. Finally, the dissolution profiles of two more promising formulations were also obtained

Preventing Home Medication Administration Errors.

Medication administration errors that take place in the home are common, especially when liquid preparations are used and complex medication schedules with multiple medications are involved; children with chronic conditions are disproportionately affected. Parents and other caregivers with low health literacy and/or limited English proficiency are at higher risk for making errors in administering medications to children in their care. Recommended strategies to reduce home medication errors relate to provider prescribing practices; health literacy-informed verbal counseling strategies (eg, teachback and showback) and written patient education materials (eg, pictographic information) for patients and/or caregivers across settings (inpatient, outpatient, emergency care, pharmacy); dosing-tool provision for liquid medication measurement; review of medication lists with patients and/or caregivers (medication reconciliation) that includes prescription and over-the-counter medications, as well as vitamins and supplements; leveraging the medical home; engaging adolescents and their adult caregivers; training of providers; safe disposal of medications; regulations related to medication dosing tools, labeling, packaging, and informational materials; use of electronic health records and other technologies; and research to identify novel ways to support safe home medication administration.

Formulation and evaluation of natural antitussive cough syrups.

Among respiratory complications, cough is an important defensive pulmonary reflex that removes fluids, irritants or foreign substances from the respiratory tract. Rosa damascene Mill, petal extract is a traditional medicine and reported to use in the management of cough. In the present study rose petals extract samples were used to prepare natural antitussive cough syrups containing ivy leaf extract to observe synergistic effect of rose water in managing coughing in rats. Four cough formulations (A1, A2, A3 and A4) were prepared. The antitussive activity was observed at three dosage levels; 5ml, 10ml and 15ml. Cough was induced by the standard procedure using sulfur dioxide gas and ammonia. The antitussive activity was recorded by observing the coughing bouts. The result indicated that all formulations had a good effect on cough reduction at 90min but comparing the effect of formulations in all doses formulations, A2 followed by A3 and A4 at 30 minute time interval which is good in comparison with standard Diphenhydramine HCL and Dextromethorphan HBr 10ml in sulfur dioxide gas and ammonia induced cough. Hence, the results of the present study indicated the synergistic effect of rose water in the management of cough ailments.

Development of grape seed extract based formulations by using non-invasive biophysical technique and its impact on skin aging.

Given the substantial benefits of grape seed extract (GSE) in reducing oxidative stress, the study aimed development, characterization and comparative analysis of GSE-based formulations. The development entailed extraction of GSE from Vitisvinifera L. HPLC confirmed catechin, epicatechin, gallic acid, epicatechingallate and procyanidin dimers. Storage of Formulations observed, Stability & rheological parameters determined. Olive oil used as a permeability enhancer. Presence of the highest oleic acid content (65-86%) in Olive oil, skin permeability within the stratum corneum was enhanced hence better transdermal skin absorption. Using two-way ANOVA, and T-test, efficacy of formulations and impact on slowing down skin aging by countering exogenous factors of oxidative stress determined. Non-invasive biophysical technique showed emulgel substantially reduced roughness, scaliness, winkles, and sebum content by 55%, 26%, 23.9% and 30.3% respectively enhancing elasticity and hydration by 50% and 32.2% respectively. Emulsion reduced roughness, scaliness, winkles and sebum content 14%, 13%, 21% and 26.13% respectively enhancing elasticity and hydration 45.3% and 29.85% respectively. The formulations significantly offset exogenous factors of aging and impact on free radicals and oxidative stress and may be safe to incorporate bio-active botanical antioxidants for evaluation of derma cosmetic benefits in management of dehydrated and aged facial skin.

Influence of mechanical skin treatment (massage, ultrasound, microdermabrasion, tape stripping and microneedling) on dermal penetration efficacy of chemical compounds.

The influence of mechanical skin treatments (massage, ultrasound, microdermabrasion, tape stripping and microneedling) on the dermal penetration efficacy was investigated. Results show that microneedling was the most effective tool. It increased the penetration efficacy (amount of penetrated active and penetration depth) by a factor > 2. Microdermabrasion and tape stripping remove parts of the stratum corneum (SC). This reduces the barrier function and increases the penetration efficacy. Microdermabrasion removed about 23% of the SC. Tape stripping removed about 34% of the SC and thus resulted in a slightly more pronounced increase in the penetration efficacy (+31% after tape stripping and +18% after microdermabrasion). Massage and skin treatment with ultrasound decreased the penetration efficacy by about one third when compared to skin where the formulations were applied without any mechanical treatment. The penetration reducing effect is caused by mechanical stress (pressure), which reduces the thickness of the SC. The increased density of the SC is considered to decrease the intercellular space within the SC and with this the flux for chemical compounds. Therefore, massage and other mechanical treatments that increase the density of the SC should be avoided if efficient dermal penetration is required.

In vivo models to evaluate ingestible devices: Present status and current trends.

Evaluation of orally ingestible devices is critical to optimize their performance early in development. Using animals as a pre-clinical tool can provide useful information on functionality, yet it is important to recognize that animal gastrointestinal physiology, pathophysiology and anatomy can differ to that in humans and that the most suitable species needs to be selected to inform the evaluation. There has been a move towards in vitro and in silico models rather than animal models in line with the 3Rs (Replacement, Reduction and Refinement) as well as the better control and reproducibility associated with these systems. However, there are still instances where animal models provide the greatest understanding. This paper provides an overview of key aspects of human gastrointestinal anatomy and physiology and compares parameters to those reported in animal species. The value of each species can be determined based upon the parameter of interest from the ingested device when considering the use of pre-clinical animal testing.

(-)-Oleocanthal Nutraceuticals for Alzheimer's Disease Amyloid Pathology: Novel Oral Formulations, Therapeutic, and Molecular Insights in 5xFAD Transgenic Mice Model.

Alzheimer's disease (AD) is a complex progressive neurodegenerative disorder affecting humans mainly through the deposition of Aß-amyloid (Aß) fibrils and accumulation of neurofibrillary tangles in the brain. Currently available AD treatments only exhibit symptomatic relief but do not generally intervene with the amyloid and tau pathologies. The extra-virgin olive oil (EVOO) monophenolic secoiridoid S-(-)-oleocanthal (OC) showed anti-inflammatory activity through COX system inhibition with potency comparable to the standard non-steroidal anti-inflammatory drug (NSAID) like ibuprofen. OC also showed positive in vitro, in vivo, and clinical therapeutic effects against cardiovascular diseases, many malignancies, and AD. Due to its pungent, astringent, and irritant taste, OC should be formulated in acceptable dosage form before its oral use as a potential nutraceutical. The objective of this study is to develop new OC oral formulations, assess whether they maintained OC activity on the attenuation of ß-amyloid pathology in a 5xFAD mouse model upon 4-month oral dosing use. Exploration of potential OC formulations underlying molecular mechanism is also within this study scope. OC powder formulation (OC-PF) and OC-solid dispersion formulation with erythritol (OC-SD) were prepared and characterized using FT-IR spectroscopy, powder X-ray diffraction, and scanning electron microscopy (ScEM) analyses. Both formulations showed an improved OC dissolution profile. OC-PF and OC-SD improved memory deficits of 5xFAD mice in behavioral studies. OC-PF and OC-SD exhibited significant attenuation of the accumulation of Aß plaques and tau phosphorylation in the brain of 5xFAD female mice. Both formulations markedly suppressed C3AR1 (complement component 3a receptor 1) activity by targeting the downstream marker STAT3. Collectively, these results demonstrate the potential for the application of OC-PF as a prospective nutraceutical or dietary supplement to control the progression of amyloid pathogenesis associated with AD.

Nanoparticulate tablet dosage form of lisofylline-linoleic acid conjugate for type 1 diabetes: in situ single-pass intestinal perfusion (SPIP) studies and pharmacokinetics in rat.

Lisofylline (LSF) is an anti-inflammatory molecule with high aqueous solubility and rapid metabolic interconversion to its parent drug, pentoxifylline (PTX) resulting in very poor pharmacokinetic (PK) parameters, necessitating high dose and dosing frequency. In the present study, we resolved the physicochemical and pharmacokinetic limitations associated with LSF and designed its oral dosage form as a tablet for effective treatment in type 1 diabetes (T1D). Self-assembling polymeric micelles of LSF (lisofylline-linoleic acid polymeric micelles (LSF-LA PLM)) were optimized for scale-up (6 g batch size) and lyophilized followed by compression into tablets. Powder blend and tablets were evaluated as per USP. LSF-LA PLM tablet so formed was evaluated for in vitro release in simulated biological fluids (with enzymes) and for cell viability in MIN-6 cells. LSF-LA PLM in tablet formulation was further evaluated for intestinal permeability (in situ) along with LSF and LSF-LA self-assembled micelles (SM) as controls in a rat model using single-pass intestinal perfusion (SPIP) study. SPIP studies revealed 1.8-fold higher oral absorption of LSF-LA from LSF-LA PLM as compared to LSF-LA SM and ~5.9-fold higher than LSF (alone) solution. Pharmacokinetic studies of LSF-LA PLM tablet showed greater Cmax than LSF, LSF-LA, and LSF-LA PLM. Designed facile LSF-LA PLM tablet dosage form has potential for an immediate decrease in the postprandial glucose levels in patients of T1D.

The efficacy of different vitamin D supplementation delivery methods on serum 25(OH)D: A randomised double-blind placebo trial.

BACKGROUND: The use of vitamin D supplementation has increased due to greater recognition of widespread deficiency. AIMS: There has been little research on the effectiveness of different delivery methods and therefore the aim of was to test the efficacy of different delivery methods on serum 25(OH)D. METHODS: Using a randomised repeated measures double-blind placebo design (registered under ClinicalTrials.gov Identifier no. NCT03463642), changes in serum 25(OH)D over a 4-week period using a capillary spot method were monitored. 62 female participants blindly chose a number related to a supplementation delivery method: pill placebo, pill, oral liquid, oral liquid placebo, Skin oil application (SOA) placebo, SOA plus vitamin D3 suspension, or SOA plus vitamin D3 suspension with essential oil enhancer; active vitamin D supplements contained 100,000IU. Participants took their allocated supplements over a 24-hr period with serum 25(OH)D retested 4 weeks later. Liquid chromatography-tandem mass spectrometry method was applied to dried blood spot samples by an independent laboratory. RESULTS: ANCOVA reported a significant difference between the groups (F1,6 = 146.68; p < 0.001, eta2 = 0.51). Separate analysis within the delivery methods (pill, SOA, oral liquid) indicated significant differences between the active and placebo supplementation groups (p < 0.01). Post hoc analysis of absolute changes indicated vit D pill and SOA + vit D + essential oil had significant increases (p < 0.05) in serum 25(OH)D compared to all other interventions with no significant difference between them. CONCLUSIONS: In human participants vitamin D oral pill has the greatest effect on serum 25(OH)D levels. Skin oil application delivery of vitamin D using a penetrator enhancer has also been shown to be an effective method of delivery.

Development and Evaluation of Oleanolic Acid Dosage Forms and Its Derivatives.

Oleanolic acid is a pentacyclic triterpenoid compound that exists widely in medicinal herbs and other plants. Because of the extensive pharmacological activity, oleanolic acid has attracted more and more attention. However, the structural characteristics of oleanolic acid prevent it from being directly made into new drugs, which limits the application of oleanolic acid. Through the application of modern preparation techniques and methods, different oleanolic acid dosage forms and derivatives have been designed and synthesized. These techniques can improve the water solubility and bioavailability of oleanolic acid and lay a foundation for the new drug development. In this review, the recent progress in understanding the oleanolic acid dosage forms and its derivatives are discussed. Furthermore, these products were evaluated comprehensively from the perspective of characterization and pharmacokinetics, and this work may provide ideas and references for the development of oleanolic acid preparations.

Preparation and antihepatotoxicity activity of Fagonia indica extract and its solid dispersion formulation.

This study aimed to evaluate and compare the antihepatotoxicity effect of Fagonia indica extract and its solid dispersion formulation (SD) against paracetamol-induced hepatotoxicity in rats. Dried Ethanolic plant extract was prepared by cold maceration in ethanol followed by solvent evaporation under reduced pressure. Quality control of crude extract was performed and the total phenolic and flavonoid contents were determined. Solid dispersion (SD) formulations were prepared by solvent evaporation technique and optimized with respect to drug solubility. Antihepatotoxicity activities of Fagonia indica extract and optimized solid dispersion were performed against paracetamol-induced hepatotoxicity in rats. Quality control parameters like total ash, acid insoluble ash, water soluble ash, crude fiber content and moisture content were within the acceptable limits. Total flavonoid and phenolic contents were found to be 31.289mg quercetin equivalents/g and 40.28mg gallic acid equivalent/g respectively. TLC Investigation of the plant extract revealed the presence of gallic acid, kaempferol and quarcetin. Optimized SD formulation with 200 mg of the dried extract, 350mg of PEG 4000 and 50mg of Tween 20 showed almost four-fold increasing in the solubility of the extract in water. The average hydrodynamic diameter of extract particles was reduced from 1972 nm to 437.6nm when prepared as SD. SD formulation showed highest antihepatotoxicity activity compared with plain plant extract at the same concentration. Optimized SD formulation at 500mg dose showed complete recovery from hepatotoxicity induced by paracetamol in rats. Therefore, SD is found to be one of the promising strategy to enhance the antihepatoxicity activity of Fagonia indica plant.

Analysis of clinical trials of new drugs in China as of 2019.

The research and development (R&D) of new drugs indicates scientific progress and economic development. However, little is known regarding ongoing or recent clinical trials in China. We analyzed data from clinical trials published before December 31, 2019, and found that the annual registration numbers are increasing annually in the country. Based on clinical indications, most tested drugs target cancers, nervous system, infections, and the cardiovascular system. Furthermore, clinical trials are mostly concentrated in Beijing, Shanghai, and Jiangsu, and conducted by large pharmaceutical companies, with multiple trials for several generic drugs. Going forward, it will be necessary to promote R&D in China of clinically relevant innovative drugs, drug delivery systems, and novel traditional Chinese medicine (TCM) and biological products, as well as to have a balanced distribution of clinical trials to sustainably meet public health needs.

Influence of Different Dosage Forms on Pharmacokinetics of 6 Alkaloids in Raw Aconiti Kusnezoffii Radix (Caowu) and Chebulae Fructus- (Hezi-) Processed Caowu by UPLC-MS/MS.

PURPOSE: To study the pharmacokinetics of the 6 alkaloids (aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine, and benzoylhypaconine) in raw Aconiti Kusnezoffii Radix (Caowu) (RC) and Chebulae Fructus- (Hezi-) processed Caowu (HC) in the rats being, respectively, administrated with RC and HC in the dosage forms of powder and decoction and to demonstrate the mechanism of detoxification of HC. METHODS: The rats were randomly divided into 4 groups and, respectively, given RC powder, HC powder, RC decoction, and HC decoction by intragastric administration. The contents of the 6 alkaloids in the plasma of the rats were detected at different time points by the UPLC-MS/MS method, and DAS 3.2.7 software was used to calculate, compare, and analyze the detected pharmacokinetic parameters. RESULTS: Compared with those of the RC powder, the values of AUC0-t and C max of the HC powder were all reduced, whereas the values of t 1/2z and T max were mostly increased. Compared with those of the RC powder, the values of AUC0-t , C max, and t 1/2z of the RC decoction were decreased and the value of T max of the RC decoction was increased. Compared with those of the RC decoction, the values of AUC0-t , t 1/2z , and C max of the diester diterpenoid alkaloids of the HC decoction were all increased. However, there was no marked difference between the pharmacokinetic parameters of the HC powder and the HC decoction. CONCLUSIONS: A decrease in the level of absorption and in the rate of elimination of the alkaloids can be detected when HC is administrated in the dosage form of the powder, explaining that in traditional Mongolian medicine (TMM), the purpose of using HC in the dosage forms of pills and powder is for decreasing the toxicity and prolonging the efficacy duration of HC. Decocting can greatly decrease the plasma concentration of the diester diterpenoid alkaloids in RC and increase their rate of elimination. The influence of decocting on RC is greater than that on HC, explaining the rationality of the steaming and boiling methods for processing Caowu and the rationality of boiling Caowu for a longer time beforehand in preparing an herb decoction containing Caowu in TCM.

Evaluation of sedative effects of an intranasal dosage form containing saffron, lettuce seeds and sweet violet in primary chronic insomnia: A randomized, double-dummy, double-blind placebo controlled clinical trial.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Persian Medicine (TPM) has been established as a valuable source of medicinal plants for the treatment of insomnia for thousands of years. Accordingly, oil extracts from plants' parts have been widely used to alleviate central nervous system (CNS) ailments including sleep disorders. A number of preparations have been recommended by TPM for the treatment of insomnia. Among them, an intranasal formulation containing oily macerates of Viola odorata L., Crocus sativus L. and Lactuca sativa L. stands out. AIM OF THE STUDY: In the present double-dummy, double-blind placebo controlled clinical trial, we aim to evaluate the effectiveness of a combination of violet oil, saffron oil, and lettuce seeds oil nasal drop compared with the placebo (sesame oil). MATERIALS AND METHODS: Fifty patients with primary chronic insomnia were randomly assigned in TPM-treatment or placebo groups, received either two drops of the herbal oil or placebo into each nostril every noon and evening for 8 weeks. Before the study commencement and after 1, 4 and 8 weeks of treatment, Insomnia Severity Index (ISI) and Pittsburgh Sleep Quality Index (PSQI) questionnaires were completed by all patients. The primary outcome measure was considered as any changes in ISI scores between the first visit and after 8 weeks. Changes in PSQI scores during the study and possible side effects were also assessed. The multicompound herbal oil was standardized using HPLC analysis and contained 0.02 mg/mL crocin and 4 µg/mL isoquercitrin. RESULTS: Our study revealed a significant reduction in the ISI and PSQI scores from baseline by the study endpoint (P ≤ 0.01). The mean ISI scores in week 8 decreased significantly for the intervention group (P = 0.001) and also the placebo group (P < 0.01) when compared with baseline. Moreover, the use of hypnotic drugs in the intervention group was significantly reduced (P < 0.001), while in the control group was maintained at baseline level. CONCLUSIONS: It seems that intranasal use of the multi-herbal preparation can be used to improve chronic insomnia and to reduce the dose of conventional hypnotic medications in insomniac patients.

Absorbable antibiotic beads as an adjuvant therapy in treating ventricular assist devices driveline infection: A case report.

BACKGROUND: Ventricular assist devices driveline infections are common, recalcitrant, and carry high morbidity and mortality. Herein, we reported a patient with driveline infection that was successfully treated with a combination of systemic antibiotics, surgical debridement, and instillation of absorbable antibiotic beads to the wound bed. METHODS AND RESULTS: A 39-year-old man with nonischemic cardiomyopathy underwent insertion of a continuous flow left ventricular assist device. Four years postoperatively, the patient presented with clinical, laboratory, and radiologic signs of driveline tract infection. He underwent extensive surgical debridement, installation of absorbable antibiotic beads that consisted of calcium sulfate, vancomycin, and tobramycin, into the wound bed, and systemic antibiotics. The patient was free of infection 9 month postoperatively. CONCLUSION: Absorbable calcium sulfate antibiotic beads may serve as a beneficial adjunct to surgical debridement and systemic antibiotics for the treatment of ventricular assist device driveline infection, and merit further investigation.

Oral intermittent vitamin D substitution: influence of pharmaceutical form and dosage frequency on medication adherence: a randomized clinical trial.

BACKGROUND: To assess adherence to and preference for vitamin D substitution with different pharmaceutical forms and frequencies of administration. METHODS: A focus group of stakeholders aimed at preparing the design of an interventional, randomized, cross-over study with 2 × 2 groups obtaining monthly or weekly vitamin D products in liquid or solid form for 3 months each. Dosage corresponds to cumulated amount of recommended 800 IU daily (5.600 IU weekly / 24.000 IU monthly). Main inclusion criteria were a vitamin D serum value < 50 nmol/l and age ≥ 18 years. Primary endpoint was adherence, secondary endpoints were preferences and vitamin D serum levels. RESULTS: The focus group reached consensus for preference of a monthly administration of solid forms to adults. Full datasets were obtained from 97 participants. Adherence was significantly higher with monthly (79.5-100.0%) than weekly (66.4-98.1%) administration. Vitamin D levels increased significantly (p < 0.001) in all participants. An optimal value of > 75 nmol/l was achieved by 32% after 3 months and by 50% after 6 months. Preferred formulation was solid form (tablets, capsules) for 71% of participants, and preferred dosage frequency was monthly for 39% of participants. CONCLUSIONS: Monthly oral vitamin D in solid form lead to the highest adherence, and is preferred by the participants. However, only one third of study participants achieved values in the optimal range of > 75 nmol/l cholecalciferol using weekly or monthly administration providing an average daily cholecalciferol dose of 800 IU. TRIAL REGISTRATION: NCT03121593 | SNCTP000002251 . Registered 30. May 2017,. Prospectively registered.

A randomized controlled study for Yuanhu Zhitong dropping pills in the treatment of knee osteoarthritis.

BACKGROUND: Knee osteoarthritis (KOA) is a common chronic disorder of knee and the leading cause of pain in the elderly with an overall prevalence of 50% in people over 60 years of age. This disease is an important factor affecting the quality of life of middle-aged and elderly people, and its main symptom is knee joint pain. Due to the pain, the knee joint activity function is limited, bringing great pain to patients, affecting their quality of life, effective prevention, and treatment of KOA is a modern medical problem. METHODS: The 60 patients who met the inclusion criteria were randomly divided into the treatment group and the control group. In this study, single center, randomized control and equivalent clinical trial were used for treatment. The treatment group received Yuanhu Zhitong dropping pills within 4 weeks, and the control group received diclofenac sodium sustained-release capsule treatment within 4 weeks. The main measures were visual analogue scale (VAS), WOMAC osteoarthritis index score and gastrointestinal symptoms rating scale (GSRS).Secondary measures included biochemical markers and adverse reactions during treatment. RESULT: The results of this trial will be published on the website of China Clinical Trial Registration Center (http://www.chictr.org.cn/searchprojen.aspx) and in peer-reviewed journals or academic conferences. CONCLUSIONS: This study is to assess the efficacy and safety of Yuanhu Zhitong dropping pills for knee osteoarthritis (KOA). REGISTRATION: PROSPERO (registration number ChiCTR1900024712).

Efficiency of Vitamin D Supplementation in Healthy Adults is Associated with Body Mass Index and Baseline Serum 25-Hydroxyvitamin D Level.

Vitamin D (VitD) has a critical role in phosphorous-calcium metabolism as well as an important role in the immune system. In the human body, VitD is synthesized as cholecalciferol in the skin, but this process requires sunlight (UVB) radiation. Numerous reports showed high prevalence of VitD deficiency, particularly during the winter season, indicating the importance of VitD supplementation. Various factors can affect the absorption of VitD, including dosage and formulation. The primary study objective was to examine the efficiency of supplementation with three different formulations containing cholecalciferol in comparison with the control group. The secondary objective was to identify other factors affecting increase in serum 25-OH-VitD. A randomized controlled intervention study was conducted in Slovenia during wintertime (January- March) on 105 apparently healthy subjects (aged 18-65 years) with suboptimal VitD status (25-OH-VitD 30-50 nmol/L). Subjects were randomized into four groups: three treatment groups receiving (A) capsules with starch-adsorbed VitD, (B) oil-based Valens VitD oral spray, or (C) water-based Valens VitD oral spray and a control group (D) which did not receive supplemental VitD. Two months of supplementation with cholecalciferol (1000 IU; 25 µg daily) resulted in significant increase in serum 25-OH-VitD levels in comparison with control group (pooled Δc 32.8 nmol/L; 95% CI: 23.0, 42.5, p < 0.0001). While we did not observe any significant differences between the tested formulations, the efficiency of supplementation was associated with body mass index and baseline serum 25-OH-VitD level. Higher supplementation efficiency was observed in participants with normal body weight (BMI < 25) and in those with more pronounced VitD insufficiency. We also determined that tested dosage was not sufficient to achieve recommended 25-OH-VitD levels in all subjects.

Are Vitamin D3 Tablets and Oil Drops Equally Effective in Raising S-25-Hydroxyvitamin D Concentrations? A Post-Hoc Analysis of an Observational Study on Immunodeficient Patients.

BACKGROUND: Vitamin D3 supplements are available as tablets or oil drops, but there is no consensus as to whether either of these preparations is more effective than the other. METHODS: We compared the effectiveness of tablets versus oil in raising S-25-hydroxyvitamin D (S-25-OHD) in plasma by re-analyzing data from a previously performed observational study in which immunodeficient patients with S-25-OHD concentrations <75 nmol/L were randomly prescribed vitamin D3 tablets (1600 IU/day) or vitamin D3 oil-drops (1500 IU/day) for twelve months. Tablets and oil were compared for the effect on S-25-OHD concentrations after 3-5 months and antibiotic use. RESULTS: Data on S-25-OHD after ≥ 3 months was available for 137 patients treated with tablets and 69 with oil drops. Both groups exhibited a significant increase in S-25-OHD-oil-drops from 55 to 86 nmol/L and tablets from 52 to 87 nmol/L-with no difference between groups (p = 0.77). In a subgroup of patients without immunoglobulin replacement, vitamin D3 supplementation with oil drops (n = 34) but not with tablets (n = 60) resulted in significantly lower antibiotic administration (p < 0.001 and p = 0.58). CONCLUSION: Vitamin D3 supplementation with tablets and oil drops were equally efficient in raising S-25-OHD concentrations. Only oil drops caused a reduction in antibiotic consumption in immuno-deficient patients who did not receive immunoglobulin replacement.