Pass Metabolism Research Articles

Design and Evaluation of Solid Lipid Nanoparticle Loaded Transdermal Patch of Nisoldipine: In Vitro, Ex Vivo and In Vivo Evaluation

The objective of the research work is to develop and evaluate the solid lipid nanoparticles (SLNs) loaded matrix type transdermal patch of Nisoldipine (NSD). SLN formulations were developed and evaluated for particle size, zeta potential, polydispersibility index, drug content, entrapment efficiency then optimized formulation was freeze dried and incorporated into a transdermal patch. The physicochemical interaction between Nisoldipine and polymer was examined by DSC (differential scanning calorimetry) and FTIR (Fourier Transform Infrared Spectroscopy). Prepared patches were measured for thickness, uniformity of weight, folding endurance, moisture content, moisture absorption. The in-vitro and ex-vivo permeation of the Nisoldipine of the patches was studied by Franz diffusion cells. In vivo bioavailability study was performed using male wistar rats for optimized formulation N6 and compared with reference tablet (Sular). Dynasan 114 lipid (N-D4, formulation) is found to produce SLNs with low size and high entrapment efficiency. SEM analysis showed non aggregated spherical particles. N6(Formulation) patch containing 8% citral showed 96.5% of drug release and higher flux with 2.17 enhancement ratio (ER). Relative bioavailability of the test formulation with respect to market formulation was considered to be 2.52. The SLN loaded transdermal patches of Nisoldipine were developed successfully. There was considerable increase in bioavailability of the test formulation (N6) when compared to the marketed formulation. The increase may be attributed to avoidance of first pass metabolism of Nisoldipine which occurs through oral administration.

Effects of Various Emulsifying Agent and Permeability Enhancer on Percutaneous Absorption of Novel Microemulsion-Based Cream

Terbinafine hydrochloride is an antifungal drug used in the treatment of fungal infections. The oral use of terbinafine hydrochloride is not recommended as it has many potential side effects and undergoes hepatic first pass metabolism. Topical route of application has a great potential as an effective and safe way to administer drug for its antifungal in effect. The concentration of surfactant and permeation enhancer significantly affects the critical parameters of cream formulation like flux, cumulative amount released at 12 hours and enhancement ratio. In vitro permeation study across rat epidermal membrane showed that menthol enhanced the transdermal absorption of drug from cream formulation. The topical cream formulation developed in this study holds the promise for the further in vivo studies. The aim of the present work under investigation is to check the effects of emulsifying agents (Cremophor RH40, Tween 60) and permeation enhancers (l-Menthol) on cream. Developing a formulation that is safe and can deliver the drug locally in an effective concentration for its effect. The development of topical antifungal drug delivery systems designed to have localized effects appears to be very advisable and beneficial over conventional routes of provides the drug administration. However, due to the relative impermeability of the stratum corneum, which principal resistance to percutaneous absorption, extensive studies are generally necessary in order to optimize both the release of the drug from the topical vehicle and skin permeation further, A topical formulation must be both physically and chemically stable, this require numerous excipients. Aesthetically pleasing, in addition to being properties, hence they play emulsifying agents and permeation enhancers have major influence on these important role.
 Keywords: Emulsifying agents, Permeation enhancers, Stratum corneum, Antifungal, Topical cream

Formulation and Characterization of Buccal Patches of Oxaceprol

Background: Oxaceprol is an anti-inflammatory and antirheumatic agent. Buccal route has advantage over conventional mode of drug administration. It avoids hepatic first pass metabolism and improve patient compliance. The main objective of the present study is to formulate and evaluation of buccal patches of Oxaceprol to overcome drawbacks of conventional dosage forms. Buccal patches were prepared by solvent-casting method using HPMC K-15 and PEG as plasticizer. Oxaceprol was initially characterized for its preliminary studies such as organoleptic properties, melting point, solubility, UV Spectroscopy, and FTIR studies. Drug-excipients compatibility was confirmed by FTIR, DSC and assay of drug content. The formulations were prepared and evaluated for parameters like physical appearance, thickness, weight uniformity, % moisture loss, folding endurance, drug content uniformity. All prepared patches of drug were smooth and elegant in appearance. No visible cracks were observed. All formulations were uniform in weight, thickness, and drug content. The folding endurance was increased with an increased in polymer concentration. In vitro drug release of F6 batch was 93.78% at the end 8 hr. Oxaceprol buccal patches showed enhanced the bioavailability. Release exponent n value obtained from Kors Meyer- Peppa’s equation was within 0.5 -1.0 which indicates anomalous release.

Formulation and Characterization of Oleogel as a Topical Carrier of Azithromycin

This study aims to formulate azithromycin oleogel to locally treat skin infections such as acne vulgaris and skin wound infection. Providing a form of azithromycin that can be administered topically is highly desired to prevent unwanted systemic complications including diarrhea, nausea, and abdominal pain. Additionally, it will avoid first pass metabolism, improves patient acceptance, provides an alternative in nauseated patients, decreases the dose by direct contact with the pathological site, and provides a noninvasive and convenient mode of administration. Furthermore, for treating wound infections, the gel will act as a scaffold biomaterial for wound closure besides its antibacterial effect. Herein, we propose the use of grapeseed oil-based oleogel with glycerol monostearate (GMS) as an organogelator as a promising strategy for the effective topical delivery of azithromycin. A series of oleogels were prepared by varying concentrations of organogelators namely GMS, palmitic acid, Compritol 888, and stearic acid, while maintaining the weight ratio of grapeseed oil and clove oil constant. Initial evaluation showed azithromycin oleogel with 15% GMS to be the optimum formulation and it was selected for further evaluation. In vivo testing of the formulated gel showed significant effectiveness in promoting faster clinical healing of Staphylococcus aureus infected wounds. The findings of the present study suggest that azithromycin oleogel is stable, safe, cost-effective, and it provides significant antibacterial activity.

Transdermal Drug Delivery System

(TDDS), additionally called ‘ Transdermal patches,’ square measures dose form design to deliver a The human skin is readily accessible surface for drug delivery. Transdermal Drug Delivery Systems therapeutically effective quantity of drug across a patients skin. In order to deliver therapeutics agents through the human skin for systemic effect, the comprehensive morphological , biophysical and physicochemical properties of the skin are to be considered. Transdermal delivery provides a leading edge over injectables and oral routes by increasing patients compliance and avoiding first pass metabolism respectively. Transdermal delivery not only provides controlled, constant administration of the drug, but also allows continuous input of drugs with short biological half-lives and eliminates pulse entry into systemic circulation, which often causes undesirable side effects. Over the past decades, developing controlled drug delivery has become increasingly important in the pharmaceutical industry. The human skin surface is known to contain, on an average,10-70 hair follicles and 200-250 sweat duct on every square centimeters of the skin area. Skin penetration enhancement techniques have been developed to improve bioavailability and increase the range of drugs for which topical and transdermal delivery is viable option. The present review article explores the overall study on transdermal drug delivery (TDDS) which leads to novel drug delivery system(NDDS).

Effect of quaternary ammonium surfactant on<em> </em>buccal permeation of budesonide film formulation: <em>in silico</em> docking studies

Budesonide, an immunosuppressant glucocorticosteroid generally used to ameliorate chronic inflammation. Low bioavailability due to first pass metabolism decreases its therapeutic activity. The present study focuses on the formulation of a biodegradable buccoadhesive film for improvement of buccalpermeation. Transparent buccoadhesive films were prepared by incorporating budesonide in HPMC matrix with triethalonamine as a plasticizer and a number of surfactants. Absence of the characteristic drug melting peak at 252°C in Differential Scanning Calorimetry (DSC) thermogram study confirmed almost complete amorphization of the drug to a homogenous solid-solid mixture in the film. The characteristic Fourier-Transform Infrared Spectroscopy (FTIR) peak of pure drug showed the carbonyl stretching in between 1600–1900 cm −1 and C–O stretching at 1095 cm −1 . Broadening of C–O stretching and masking of carbonyl stretching confirmed the drug polymer interaction. In vitro dissolution and ex-vivo buccal tissue permeation revealed upto 72% and more than 58% respectively using surfactants upto 6 hour of study. Enhanced buccal permeability and flux were found in presence of surfactant compared to its absence. New film formulation could be developed including surfactant for improved buccal permeation with expected increased bioavailability. The in silico study confirmed about a stable interaction between drug and polymer (−3.1 kcal/mol).

Design and characterization of fast dissolving buccal film of imipramine HCL

In depressed individuals, Imipramine exerts a positive effect on mood. TCAs are potent inhibitors of serotonin and norepinephrine reuptake. Imipramine hydrochloride having variable bioavailability i.e. ranging from 29-77% due to first pass metabolism, peak plasma concentration is usually attained 2-6 hours. Absorption is unaffected by food. It is freely soluble in water. The objective of this research work is to improve the bioavailability of the drug and fast the onset of action to decrease the depressant activity. The Buccal bioavailability of Imipramine HCL is only 29-77% for this reason drug can be administered into Buccal mucosa using mucoadhesive film. It can be made fast drug release and directly enter into blood circulation through Buccal mucosa and increase the drug bioavailability. Fast dissolving Buccal films were prepared by solvent casting method using various polymers like hydroxyl propyl methyl cellulose E15, PVP, PVA and sodium saccharin, plasticizer and vanillin as flavouring agent. Dissolution profile as studied in USP dissolution apparatus type 1 using pH 6.8 simulated saliva. The influence of variable like polymer type and concentration on Imipramine HCL release profile was studied. The formulation was optimized on the basis of various evaluation parameters like drug content and in vitro drug release. Formulation F3 successfully fast the release of drug within 8 minutes. The IR Spectra revealed the absence of interaction between drug and selected polymer, results of stability studies were as per ICH guide lines and results indicated that the selected formulation was stable.

Formulation and evaluation of mouth dissolving film of antihypertensive agentFormulation and evaluation of mouth dissolving film of antihypertensive agent

Mouth dissolving film is the one of the most advanced oral solid dosage form because of its flexibility and comfort in use. Mouth dissolving films are oral solid dosage form that disintegrate and dissolve within a minute when placed in mouth without taking water or chewing. This dosage form allows the medication to bypass the first pass metabolism so bioavailability of medication may be improved .Mouth dissolving film has potential to improve onset of action lower the dosing and eliminate the fear of chocking. Formulation of mouth dissolving films involves both the visual and performance characteristics as plasticized hydrocolloids, API taste masking agents are being laminated by solvent casting and semisolid casting method. Solvent casting method being the most preferred method over other methods because it offers great uniformity of thickness and films prepared having fine glossy look and better physical properties. Mouth dissolving films are evaluated for its various parameters like thickness, physical property like folding endurance, disintegration and dissolution time. This review gives an idea about formulation techniques, evaluation parameters, overview on packaging and some available marketed products of mouth dissolving films.

A Novel Tool for Controlled Delivery: Transdermal Drug Delivery System

Transdermal Drug Delivery Systems comes under the category of Controlled drug delivery. The main goal of TDDS is to deliver the drug through skin into systemic circulation at controlled rate. TDDS is used to overcome the problems faced during drug administration through oral route. TDDS offers various advantages over different types of drug delivery like oral, IV etc. it provides control release of drug, avoids first pass metabolism, improves bioavailability, better patient compliance and many more. Drug with small molecules can be easily given by transdermal route. These Transdermal patches represents key outcome for growth in skin science and technology. This Review article explains all the detailed information of introduction of TDDS, its advantages and disadvantages, skin and drug permeation and its principle, contents of Transdermal patches it's types and evaluation test.

PSAT050 An Unusual Case of Adrenal Insufficiency After Using Budesonide for Treatment of Microscopic Colitis

Abstract Introduction Long term use of systemic glucocorticoids are a common cause of secondary adrenal insufficiency from 1.4-27.5% of cases. On the other hand, Budesonide, a non-halogenated steroid that is widely used for its low systemic absorption is rarely reported to cause secondary adrenal insufficiency. Case A 39-year-old female with significant medical history of anxiety, bipolar disorder, hypothyroidism, type 2 DM and lymphocytic colitis was admitted to the hospital with acute mental status change and lethargy. She reported a 3-week history of diffuse abdominal pain and diarrhea. She endorsed weight loss but denied any fever, vomiting, recent infection or any significant history of hepatitis. In ER, her vitals were notable for a BP of 105/68 mm Hg, Pulse 76 beats/min, temperature 97.5F, pulse oximetry 100% with 2 L nasal canula. On examination she appeared frail, alert but mildly confused. Admission labs showed sodium 143, potassium 4.3, bicarbonate 15, creatinine 1.2, GFR 57, blood glucose 67, Hemoglobin 6.3 and WBC 4.3, UA negative. During the ER course she became hypotensive with SBP in 80s. She was fluid resuscitated with a total of 4 L of normal saline and was eventually started on vasopressor support due to profound hypotension unresponsive to fluids. One unit of PRBC was transfused and she was transferred to MICU for further monitoring. Baseline cortisol level was drawn, and she was started on dexamethasone for presumed adrenal insufficiency, while awaiting the result of her labs. Her cortisol was subsequently confirmed to be 5.5mcg/dl. She was maintained on stress dose steroids and experienced dramatic improvements in her clinical status and BP. A review of her medical history revealed that she was diagnosed with microscopic colitis 5 months prior to the current admission and had been placed on budesonide 9mg/day, tapered slowly to the current dose of 3mg/day. She reported compliance with her budesonide up to the date of the admission. Discussion Iatrogenic adrenal insufficiency from Budesonide is rarely reported in the literature. Budesonide is a common choice for IBD, especially Crohn's disease and microscopic colitis. It has a high first pass metabolism (80-90%), thus limiting its systemic bioavailability to as low as 9-21%. Despite that, a few cases of chronic oral Budesonide use resulting in AI have been reported. As it is metabolized in the liver via CYP450 isoenzymes, concurrent use of CYP450 inhibitors or hepatic cirrhosis can also potentially interfere with its metabolism and increase its systemic bioavailability. According to literature there have been a few descriptions of patients developing AI without prior liver disease, similar to our patient. Caution should therefore be exercised in prescribing budesonide and physicians should have a high index of suspicion when patients on budesonide present with symptoms suggestive of adrenal insufficiency. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

The Impact of Pharmacogenomic CYP3A5 Variants on Calcineurin Inhibitor Metabolism and SLCO1B1 Variants on Methotrexate in Adult Allogeneic BMT Patients

Allogeneic blood and marrow transplant (BMT) is used to transplant a new immune system in patients with hematologic malignancies or immune-mediated disease. BMT patients require initial immune suppression to prevent graft rejection and graft versus host disease (GVHD). Tacrolimus and cyclosporine are calcineurin inhibitors (CNI) and methotrexate is an antimetabolite used to mitigate this immune response. Tacrolimus has data supporting oral dose variation based on pharmacogenomic (PGx) studies for Intermediate Metabolizers (IM) and Poor Metabolizers (PM) on studies done in kidney transplant patients. There are fewer studies on BMT patients in this field, and even less on the variability of IV to oral conversion dosing and first pass metabolism effect based on PGx profiles. Methotrexate has been shown to have PGx mutations affecting its metabolism at higher dosing used for chemotherapy, but its impact on BMT patient dosing is not well-defined. Based on our study, we found statistically significant variability in Tacrolimus concentration based on drug assay levels compared with dosing for Intravenous (IV) and oral formulation based on PGx predicted phenotypes. We further noted a profound effect on first pass metabolism when transitioning between IV and oral dosing of Tacrolimus based on PGx predicted phenotypes. The average oral dose in predicted IM phenotypes divided by the IV dose was 2.68. For the predicted PM phenotype, the average oral dose divided by the IV dose was 1.18. The p-value in a two-tailed nonparametric T-test with equal variance assessing the conversion factor from IV to oral dosing in predicted IM versus PM phenotypes was significant with a p-value of 0.002. Methotrexate metabolism did not seem to be affected by PGx mutations at the doses used for BMT GVHD prevention.

Prednisone is 100% converted to Prednisolone by first pass metabolism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

A Review on Transdermal Patches

Since the start of life on the earth, humans have applied plenty of substances to their skin as cosmetics and therapeutic agents. However, it was the 20 th century once the skin became used as route for future drug delivery.Today about two third of drugs (available in market) are taken orally, but these aren’t as effective as required. To enhance upon the features the transdermal drug Delivery system was emerged. Amongst all techniques that transdermal drug delivery systems (TDDS), also referred to as “patches,” are dosage forms designed to deliver a therapeutically effective quantity of drug across a patient’s Skin. It give controlled continuous delivery of drugs via the skin to the systemic circulation. Advantage of transdermal drug delivery system are limitation of hepatic first pass metabolism, improvement of therapeutic potency and maintenance of steady plasma level of the drug. transdermal patch (Skin Patch) uses a special membrane to control the rate At which the liquid drug contained in the reservoir within the patch will pass through the skin and Into the bloodstream. Drugs administered through skin patches include scopolamine (for motion sickness), nicotine (for quitting smoking), estrogen (for menopause and to stop osteoporosis after menopause), nitroglycerin (for angina), and lidocaine to relieve the pain of shingles (herpes zoster).Transdermal patches were developed in the 1970s and the first was approved by the FDA in 1979 for the treatment of motion Sickness. IN 1981, patches for nitroglycerin were approved, and today there exist variety Of patches for drugs such as clonidine, fentanyl, Lidocaine, nicotine, nitroglycerin, estradiol, Oxybutinin, scopolamine, and testosterone. There are combination patches for Contraception, also as hormone replacement. Depending on the drug, the patches typically last from 1to7days. Non-medicated patch markets include Thermal and cold patches, nutrient patches ,skin care patches. Skin patch uses a special membrane to manage the rate at which the liquid drug contained in reservoir within patch will pass through the skin and into the bloodstream. Some drugs should be combined with substances, such as alcohol, that increase their ability to penetrate the skin so as to be used in skin patch. From last twenty years over thirty five transdermal products are approved generating sale of $3.2 billion in 2002,which is predicted to rise to $4.5 billion in 2008. TDDS are adhesive drug-containing devices of defined surface area that deliver predetermined quantity of drug to the surface of intact skin at a programmed rate to reach the systemic circulation. The greatest challenge for transdermal delivery is that only a limited number of medicine are able to administration by this route.Tansdermal route of administration is reflected as one of the potential route for The local and systemic delivery of drugs. Transdermal patches provides better therapeutic effect with minimum facet effects transdermal patches are designed to release the active ingredient at a zero order rate for a period of several hours to days following application to the skin.

Formulation and Evaluation of Solid-Self Nano Emulsifying Drug Delivery System of Darunavir

The main aim of this research article is to Formulate and Evaluate the S-SNEDDS of Darunavir. Darunavir is an anti-retroviral protease inhibitor which is in use from long time, but it has poor bioavailability because of poor aqueous solubility and extensive first pass metabolism, when used in the form of conventional dosage form. As it is a BCS Class II drug, which shows low solubility and high permeability. The S-SNEDDS of Darunavir was prepared to improve its oral bioavailability and its release rate was evaluated by in vitro release. The solubility of Darunavir in various oils was to decide and identify the oil phase of formulations. Different oils, surfactants and co-surfactants were screened for their ability to emulsify the selected oil. The pseudo ternary phase diagram was used to know the self -emulsification region of formulation. The optimized S-SNEDDS formulation contain Darunavir (150mg), Caproyl®90(50mg), Labrasol® and Transcutol® mix (45 mg). The data of the FTIR confirms that there is no interaction observed and the drug and excipients was compatible with each other. The developed SNEDDS formulations were examined for nano emulsifying capabilities, and the resulting nano emulsions were investigated for self-emulsification efficiency, dispersibility and in-vitro dissolution. Centrifugation tests, particle size distribution, heating cooling cycle, zeta potential, and freeze thaw cycling were performed on the optimised formulations to establish the stability of the produced SNEDDS formulation. Further produced S-SNEDDS micromeritics studies were done. The formulation was shown to significantly improve drug release, with total drug release occurring within 60 minutes. Darunavir self-emulsifying formulation was thus effectively produced.

Natural Gums and Mucilage as Gelling agents in Topical Gel Formulation

The study was conducted to study the gelling efficiency of natural gums (tamarind seed gum) and mucilage (moringa mucilage) using ibuprofen as model drug. Topical drug delivery (TDS) eliminates first pass metabolism and improves bioavailability. Hydrogels are dispersions of network of polymer chains in water as colloidal gels. Ibuprofen an anti-inflammatory, was chosen as a model drug in the preparation of hydrogel for site targeted action and to avoid side effects. Physical properties like swelling index, solubility, loss on drying, flow properties were evaluated. Chemical characterization of isolated gum and mucilage revealed presence of polysaccharides. Ibuprofen topical gels with natural gum (tamarind seed gum (1-7%), moringa mucilage (2-8%) were compared with official xanthan gum (1-4%), guar gum (1-3%) as natural gelling agents and HPMC K4M (1-6%), HPMC K100M (1-6%) and sodium alginate (2-6%) as semi synthetic gelling agents. Drug and excipients are compatible with each other by FTIR studies. The prepared gel formulations were evaluated for clarity, homogeneity, spreadability, drug content, in-vitro diffusion, ex-vivo permeation, skin irritation and stability studies. All formulations have shown better physicochemical properties. Based on the maximum percentage of drug release, formulations containing natural polymers tamarind seed gum (5%), moringa mucilage (8%), xanthan gum (4%), guar gum (3%) were optimized. And semi synthetic polymers HPMC K4M (4%), HPMC K100M (3%), sodium alginate (6%) were optimized. NF10 formulation with guar gum (3%) is optimized based on the percentage of drug release (27.0±0.14%) for 8 hrs, flux of (427.2±0.09µg/cm2/hr), cumulative amount of drug permeated Q8 (329±1.53µg/cm²) and permeability coefficient of (17.08±1.04 ×10-3cm/hr) when compared with tamarind gum (5%), NF1 (23.8±0.13%), (290±1.04µg/cm²), (376.6±0.04µg/cm2/hr), (15.04±0.03×10-3cm/hr) and moringa mucilage (8%), NF3 (14.3±0.19%), (175±0.90µg/cm²), (227.1±0.03µg/cm2/hr), (9.08±0.02×10-3cm/hr). The drug release pattern was found to follow first order kinetics and korsemeyer peppas release mechanism with fickian diffusion release. Formulations were found to be non-irritant and stable. Tamarind gum and moringa mucilage were efficient as gelling agent in preparation of ibuprofen topical gel but showed retarding effect when compared with official guar gum.

Cutaneous/Mucocutaneous Leishmaniasis Treatment for Wound Healing: Classical versus New Treatment Approaches

Cutaneous leishmaniasis (CL) and mucocutaneous leishmaniasis (ML) show clinical spectra that can range from a localized lesion (with a spontaneous healing process) to cases that progress to a generalized systemic disease with a risk of death. The treatment of leishmaniasis is complex since most of the available drugs show high toxicity. The development of an effective topical drug formulation for CL and ML treatment offers advantages as it will improve patient’s compliance to the therapy given the possibility for self-administration, as well as overcoming the first pass metabolism and the high costs of currently available alternatives. The most common dosage forms include solid formulations, such as membranes and semi-solid formulations (e.g., ointments, creams, gels, and pastes). Topical treatment has been used as a new route of administration for conventional drugs against leishmaniasis and its combinations, as well as to exploit new substances. In this review, we discuss the advantages and limitations of using topical drug delivery for the treatment of these two forms of leishmaniasis and the relevance of combining this approach with other pharmaceutical dosage forms. Emphasis will also be given to the use of nanomaterials for site-specific delivery.

Preparation of Darunavir Cubosomal Gel to Treat HIV Infections

HIV (human immunodeficiency virus) is a virus that attacks the body's system. AIDS could be a chronic potentially life threatening condition caused by HIV. This article provides a summary of studies assessing the pharmacokinetics of antiretroviral drug Darunavir. Darunavir is a BCS class II drug which inhibits the HIV protease enzyme by forming an inhibitor-enzyme complex there by preventing cleavage of the polyproteins. This research work aims to increase the penetration of Darunavir into deeper layers of skin by formulating cubosomes of Darunavir into a genital Gel that helps in enhancing the Bioavailablity by providing first pass metabolism. Cubosomes were prepared by the Top- down approach (Emulsification method) employing GMO as a lipid phase vehicle, poloxamer 407 as a stabilizer and distill water as an aqueous phase. Darunavir is an antiretro viral drug with good bioavailablity. The prepared cubosomes were characterized by Visual examination, Entrapment efficiency, Particle size, Zeta potential, In-vitro drug release studies. Optimised formulation (F4) showed good response among all the opposite cubosomal preparation. This (F4) cubosomal prepration was made as Gel using Carbopol 974 BP,and are studied for pH, Drug content,and Diffusion studies. Among all the prepration DARf6 was found for example the utmost drug release. This novel cubosomal genital gel would be promising system for effective drug delivery.

Formulation and Evaluation of Olmesartan Medoxomil Transdermal Drug Delivery System

Transdermal patches are cutting-edge drug delivery methods that are essential to the management of many diseases. Due to the avoidance of first pass metabolism the drug molecules are delivered into the systemic circulation at a controlled and predefined pace with the help of TDDS, which also helps to achieve efficient bioavailability. This study's goal was to create matrix-type Olmesartan medoxomil transdermal patches utilizing the solvent evaporation method and various polymer ratios, including HPMC 15 cps, HPMC 5 cps, and Eudragit S 100. Plasticizers like glycerin, propylene glycol, and PEG 200 are used, along with solvents like methanol and chloroform. According to FT-IR studies, pure drugs and excipients are compatible with each other. The generated patches are assessed for their thickness, weight variation, folding endurance, moisture content, drug content, surface pH, and in vitro diffusion studies. Among all the formulations, F6 showed the best characteristic properties and in vitro drug diffusion.

“Employment of PEGylated ultra-deformable transferosomes for transdermal delivery of tapentadol with boosted bioavailability and analgesic activity in post-surgical pain”

The utilization of the proper and safe analgesics was considered a major concern in pain alleviation especially that associated with surgical procedures. Novel analgesics as Tapentadol hydrochloride (TAP) was involved efficiently instead of the common opioids to overcome the subsequent severe and common adverse effects associated with opioids utilization. Unfortunately, the extensive first pass metabolism limits the oral bioavailability of TAP and predisposes to a diminished duration of action, hence larger frequent doses of TAP will be required. Therefore, the target of this study was to lodge TAP into PEGylated transferosomes to boost its transdermal delivery. The PEGylation contemplated to boost both TAP permeability and bioavailability besides offering extra resilience to the vesicles.The impact of diverse variables on the characteristics of the vesicles and distinguishing the optimal formula were implemented adopting 23 factorial experiment via Design Expert® software. The resulted eight formulae were fabricated by thin film hydration technique, additionally they were evaluated based on the findings of entrapment efficiency percent (EE%), particle size (PS), polydispersity index (PDI), zeta potential (ZP) and the optimal one was involved in further assessments.The optimal formula (F8) exhibited spherical vesicles with EE% of 77.9 ± 3.4 %, PS of 150.5 ± 5.33 nm, PDI of 0.47 ± 0.05, ZP of −40.7 ± 4.6 mV and it also revealed greater deformability index (30.9 ± 6.1 g) relative to traditional transferosomes (12.15 ± 2.49 g).In addition, confocal laser scanning microscopy examination affirmed the superior penetration of Rhodamine B (RhB) dye thorough the rat's skin from F8 relative to the dye solution. The safety of F8 was confirmed by histopathological study. Moreover, dermato-kinetic study disclosed that TAP exhibited higher retention within the rat's skin form F8 relative to TAP dispersion. Furthermore, the in vivo pharmacodynamics activities conducted on male rats confirmed the superiority of F8 over the drug dispersion in alleviation the induced pain by IP injection of acetic acid and by formation of paw incisions.Collectively, the credibility of F8 as panel for transdermal delivery of TAP with boosted bioavailability and analgesic activity could be ensured on the basis of the obtained findings.

The complete bioavailability of asundexian is unaffected by tablet formulation, gastric pH or food

Abstract Background Anticoagulation and antiplatelet therapy, mainstays for the prevention of thromboembolic disorders, are associated with an increased bleeding risk. Asundexian, a novel, potent and reversible oral inhibitor of factor XIa, is independent of the extrinsic coagulation pathway and thus not expected to increase bleeding risk. Purpose To determine the absolute bioavailability (FAB), and to assess the impact of gastric pH modulators, tablet formulation, and food on the PK and safety of asundexian. Methods Four studies enrolled healthy White males aged 18–45 years. For FAB (20463), participants received a microdose of 50 μg stable [13C7,15N]-labelled asundexian intravenously (iv) 2 hours after 25 mg asundexian orally in the fasted state. The remaining studies randomized participants to each of 3 treatment sequences. Tablet formulation and food effects were explored in studies 19663 and 21660; participants received asundexian (immediate release [IR] vs amorphous solid dispersion [ASD] phase [Ph] 2 [19663] or ASD Ph 2 vs ASD Ph 3 [21660]) in the fasted states. Food effect was explored using the Ph 2 and Ph 3 tablets. Gastric pH modulators (omeprazole and antacid) were given with asundexian in the fasted state (20459). Blood samples were taken over 72–96 hours post dose. Key PK parameters were area under concentration/time curve (AUC; and AUC/dose [D]) and maximum observed concentration (Cmax; and Cmax/D). FAB was derived as (AUC/D)oral/(AUC/D)iv. Relative bioavailability (FR) was derived from the ratios (ASD Ph 2:IR or ASD Ph 3:ASD Ph 2) of AUC/D and Cmax/D (fasted); gastric pH modulation and food effect were derived from the ratios asundexian+pH modulator:asundexian and fed:fasted of AUC and Cmax, respectively. Results PK data were available for 59 participants. Asundexian was completely bioavailable (FAB, 103.9%). Ph 2 and Ph 3 ASD tablets exhibited a FR of 94.3% and 95.1% for AUC/D compared with the IR or Ph 2 ASD tablet, respectively. Cmax/D results were similar (95.5% and 88.7%, respectively). A high-calorie, high-fat meal reduced AUC and Cmax of asundexian to 91.1% and 78.3%, respectively (ASD Ph 2 tablet), and to 96.9% and 95.1%, respectively (ASD Ph 3 tablet). Coadministration of omeprazole had no influence on the PK of asundexian, whereas antacid slightly reduced AUC and Cmax by 10% and 16%, respectively. Geometric least-squares mean (90% confidence intervals) for the ratios of AUC(/D) and Cmax(/D) by treatment are shown in Figure 1. There were no serious adverse events (AEs) or deaths; most AEs were mild or moderate. Conclusions Orally administered asundexian was almost completely bioavailable. First pass metabolism in the gut and liver does not play an important role in the bioavailability of asundexian; there were no clinically relevant changes due to formulation, food conditions or gastric pH modulation. Results were used to guide dosing recommendations for subsequent Ph 2 (completed) and Ph 3 (planned) studies. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): BAYER AG