Rate Of Drug Absorption Research Articles

Formulation and evaluation of immediate release tablet of Cisapride

The term “immediate release” pharmaceutical formulation includes any formulation in which the rate of release of drug from the formulation or the absorption of drug, is neither appreciably, nor intentionally, retarded by galenic manipulations. These tablets which disintegrate rapidly and get dissolved to release the medicaments. It may be provided for by way of an appropriate pharmaceutically acceptable diluent or carrier, which diluent or carrier does not prolong, to an appreciable extent, the rate of drug release or absorption.

Dependence of Bioavailability on Mean Absorption Time: What Does It Tell Us?

The extent and rate of bioavailability are fundamental measures to characterize the pharmacokinetics of drugs after oral administration. Together with bioavailability (F), the mean absorption time (MAT) can be used to define the rate of bioavailability, i.e., the rate of drug absorption. Previous results suggest that F may depend on MAT. Estimates of F and MAT were obtained from the input function (sum of two inverse Gaussian functions) used to model the oral absorption process. The estimation was performed by population analysis (nonlinear mixed-effects modeling) based on data from bioavailability studies in healthy volunteers. For trospium and ketamine, F decreased significantly with increasing MAT, while for propiverine, a significant increase was observed. Thus, the interindividual variability in F could be largely attributed to the interindividual variability in MAT. For trospium and propiverine, the relative dispersion (normalized variance) of the absorption time distribution increased significantly with MAT. For trospium and propiverine, the plot of F versus MAT provides information about the effect of gastrointestinal transit on drug absorption. In contrast, an increase in hepatic extraction with increasing MAT is responsible for the dependence of F on MAT. The F versus MAT plot is suggested as a simple diagnostic tool in evaluating the results of bioavailability studies.

A Bird Eye View on Natural Gums and Mucilage used in Drug Delivery System

Natural mucilage is utilized in drug delivery systems (DDS) to accomplish a variety of duties, including directly or indirectly regulating the rate and amount of drug release in specific circumstances. Gums are biomolecules composed of carbohydrates that may attract water and form gels. Proteins and minerals are typically found in the creation of the gums. Gums exist in a number of types, including mucilage gums, seed gums, exudate gums, and others. Plant gums are among the most important gums because of their bioavailability. Excipients are being used in unique dosage forms to fill specific tasks as a result of advances in drug delivery technology. In some cases, these additives have a direct or indirect effect on the amount and/or rate of drug release and absorption. Given the present trend toward the use of natural goods derived from plants, the substitution of synthetic additives with natural ones is important. The world is getting increasingly interested in natural drugs and excipients. Natural mucilage has advantages over synthetic mucilage because it is more easily available, less expensive, and chemically inert. They now compete with several polymeric materials for use as diverse drugs and have advanced from being an excipient to cutting-edge drug carriers. Extensive research has gone into the development of safe and effective natural-based mucilage particulate drug delivery systems. Natural gums and mucilage are examined, as well as their isolation, purification, standardization, and characterization properties, as well as their applications. This article provides an overview of natural excipients used in both traditional dosage forms and innovative drug delivery systems.

On the Interplay between Machine Learning, Population Pharmacokinetics, and Bioequivalence to Introduce Average Slope as a New Measure for Absorption Rate

The scientific basis for demonstrating bioequivalence between two drug products relies on the comparison of their extent and rate of absorption. For the absorption extent, the area under the C-t curve (AUCt) is used without a doubt. For absorption rate, the maximum observed plasma concentration (Cmax) is still suggested by the authorities, despite the numerous concerns. In this study, the concept of average slope (AS) is introduced as a metric to express the absorption rate of drugs. Principal component analysis and random forest models were applied to actual and simulated two × two crossover bioequivalence studies to show that AS expresses the appropriate properties for characterizing absorption rate. Several absorption kinetics (slow, typical, fast) and sampling schemes (sparse, typical, dense) were simulated. The two machine learning algorithms, applied to all these scenarios, proved the desired properties of AS while showing the non-desired performances of other metrics currently used or proposed in the literature. The estimation of AS does not require any assumptions, models, or transformations and is as simple as that of AUCt. A modified version of AS, termed “weighted AS”, is also introduced in order to place emphasis on early time points where the C-t profile describes more clearly the absorption process.

Study on the solubilization effect of 7-ethyl-10-hydroxycamptothecin based on molecular docking and molecular dynamics simulation.

With the continuous improvement of anticancer drugs, the condition of patients has been controlled to a certain extent, but the problem that still needs to be urgently solved is that most anticancer drug candidates' solubility is low. On the one hand, the low solubility of anticancer drugs may lead to a decrease in the absorption rate of anticancer drugs, poor treatment effect, and even death in severe cases. On the other hand, it will also lead to a waste of medical resources. At the same time, the rapid and scientific screening of ideal anticancer drugs has become a difficult problem that researchers have to face in the research process. In this study, we found two kinds of SN38-ligand complexes that solubilize 7-ethyl-10-hydroxycamptothecin (SN38) through molecular docking and molecular dynamics simulation methods. This process not only provided valuable information on improving the solubility of SN38, but also helped to discover effective potential complexes that solubilize SN38 quickly and scientifically. The interaction of the SN38 with folic acid and isoproterenol hydrochloride was rapidly determined by molecular docking and molecular dynamics simulation methods. We used Discovery Studio software to perform molecular docking. And then, we used Gromacs 2019.3 software to perform molecular dynamics, analyzing and comparing the hydrogen bonds, solvent-accessible surface areas, energies, and so on between SN38 and SN38-ligand complexes. And the force field adopted the Gromos 54a7.

Advanced Herbal Technology

The newest idea in herbal medication technology, known as the "herbosome," overcomes the drawbacks of conventional drug delivery methods. Since ancient times, doctors and patients around the world have used herbal medicines extensively due to their superior medicinal value. No negative effects or less side effects than contemporary medications. The herb's active components are bonded to phospholipids in the herbosome structures. A water-soluble head and two fat-soluble tails make up the phosphor lipid's molecular structure. The phosphor lipid works well as an emulsifier due to its dual solubility. The herb in some form provides drastically higher bioavailability for lipid soluble pharmaceuticals explained by faster and better absorption when the emulsifying properties of the phospholipids are combined with the standardised botanical extracts. digestion and intestinal absorption. Herbosome technology has been successfully used to increase the bioavailability of numerous well-known herbal extracts and phyto components, including ginseng, milk thistle, green tea, grape seed, and ginkgo biloba. It can also be produced for a variety of therapeutic uses or nutritional supplements. This approach has been deemed promising for efficient and appropriate systematic drug administration since it can increase the rate and amount of drug absorption through the lipoid bio-membrane.

Relationship Between Dissolution Rate in Vitro and Absorption Rate in Vivo of Ketamine Prolonged-Release Tablets.

Understanding the processes that determine the time course of drug absorption rates is of great interest. This study aims to answer the questions: (1) How well can the in vitro dissolution rate predict the in vivo input function (absorption rate) of a prolonged-release ketamine dosage form (PR-ketamine)? (2) Is the information obtained from the in vitro dissolution rate profile useful in estimating bioavailability? In vivo plasma concentration data were obtained from 15 healthy volunteers after intravenous and oral dosing of 20 mg PR-ketamine tablets. Both the dissolution and input rates were modeled by a sum of two inverse Gaussian functions. The absorption process was dissolution-limited but the mean input time exceeded the mean dissolution time. When the delayed dissolution rate was used to fit the oral data, the estimated bioavailability was nearly identical to that obtained with the full model. The in vitro dissolution rate profile could be used to develop a one-point sampling strategy for predicting bioavailability. According to their fractional rate profiles, dissolution and input rates belong to different classes of functions. A comparison of the time course of the absorption rate with that of the dissolution rate can reveal more details of the absorption process.

Pharmacokinetic prediction of nebulised polymyxin for pulmonary delivery

Inhaled administration of polymyxin B is increasingly used to treat multi-drug resistant bacterial lung infections. However, the lack of clinical data on the pharmacokinetics of inhaled administration makes drug dose design, efficacy assessment and drug safety assessment a challenge. In this study, clinical data from intravenous injections were deconvoluted by an equal-step numerical deconvolution algorithm to derive the drug absorption rate of polymyxin B in vivo. The absorption rate was substituted into a published pulmonary absorption compartment model to predict the systemic pharmacokinetics of polymyxin B. It was demonstrated that the intravenous PK dataset with the pulmonary compartment model provided reliable estimates of the accuracy and bias of inhaled systemic pharmacokinetics.

In-vitro and in-vivo evaluation of sustained-release buprenorphine using in-situ forming lipid-liquid crystal gels

AimsSustained-release systems reduce the incidence of drug side effects and the need for frequent drug consumption, thus increasing patient compliance with treatment. In this study, we aimed to produce sustained-release buprenorphine (BP) using lipid-liquid crystal gels. Main methodsThe three experimental groups in this study included: group I: lipid-liquid crystal formulation 5 (F5) containing BP, group II: BP-free F5, group III: BP solution in NMP, and group IV: control (no treatment). The formulations were injected subcutaneously into the rabbits' back neck. Key findingsThe results showed that the time required to reach the drug's maximum concentration (Tmax) was longer in group I than in group III. The maximum BP concentration (Cmax) and the constants of the drug removal rate and drug absorption rate (Ka) were significantly higher in group III compared to group I. The half-life (t1/2) of the drug in blood circulation was significantly longer in group I than in group III. Histopathological analysis revealed no histological abnormalities in the skin and heart in group I (BP-containing F5); however, mild hyperemia was observed in interstitial vessels in group III (BP-containing NMP). The kidney and liver tissues showed normal structure in the control group, as well as groups I and II. However, in the group receiving BP-containing NMP, significant congestion, tissue damage, necrosis, and fibrosis were observed in the kidney and liver. SignificanceThe results showed that the lipid-liquid crystal system can be used to design slow-release platforms for BP, minimizing the side effects associated with the use of its conventional forms.

Paliperidone-benzamide Cocrystals: Preparation, Characterization, In Vitro/In Vivo Evaluation

Background: The current investigation contributes to the development of novel Paliperidone (PPD) co-crystals (CCs) using benzamide (BZ) as a conformer. The CCs were synthesized using the solvent evaporation technique. Methods: The enhancement in solubility was studied by saturation solubility studies. Structural characterization of CCs was performed by Fourier Transform Infra-Red Spectroscopy (FTIR), powder X-ray diffraction (PXRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM) and Proton Nuclear Magnetic Resonance (1H- FT NMR) to verify CC formation. Results: CCs exhibited a higher aqueous solubility of 2.067±0.004mg/ml when compared to pure drug 0.473±0.012mg/ml. This designated aqueous solubility enhancement of CCs by 4.36 folds. In vitro dissolution data of the CCs exhibited a drug release of 96.5±1.63% in 60min, while pure drug showed a poor release of 37.8±1.76% in the same time period In vivo studies resulted in enhanced rate and extent of drug absorption from CCs when compared to drug suspension. Conclusion: CCs formed between PPD and BZ present a novel approach in overcoming the hurdles in the solubility of PPD that exhibits poor aqueous solubility.

The risk of drug resistance during long-acting antimicrobial therapy.

The emergence of drug resistance during antimicrobial therapy is a major global health problem, especially for chronic infections like human immunodeficiency virus, hepatitis B and C, and tuberculosis. Sub-optimal adherence to long-term treatment is an important contributor to resistance risk. New long-acting drugs are being developed for weekly, monthly or less frequent dosing to improve adherence, but may lead to long-term exposure to intermediate drug levels. In this study, we analyse the effect of dosing frequency on the risk of resistance evolving during time-varying drug levels. We find that long-acting therapies can increase, decrease or have little effect on resistance, depending on the source (pre-existing or de novo) and degree of resistance, and rates of drug absorption and clearance. Long-acting therapies with rapid drug absorption, slow clearance and strong wild-type inhibition tend to reduce resistance caused by partially resistant strains in the early stages of treatment even if they do not improve adherence. However, if subpopulations of microbes persist and can reactivate during sub-optimal treatment, longer-acting therapies may substantially increase the resistance risk. Our results show that drug kinetics affect selection for resistance in a complicated manner, and that pathogen-specific models are needed to evaluate the benefits of new long-acting therapies.

Ginsenoside Rg1 Nanoparticles Induce Demethylation of H3K27me3 in VEGF-A and Jagged 1 Promoter Regions to Activate Angiogenesis After Ischemic Stroke.

Compared with traditional drugs, nanomaterial drugs have the benefits of improving the solubility, bioavailability, and absorption rate of insoluble drugs. Nanoporous complexes can increase the efficiency with which drugs can penetrate the blood-brain barrier and reach target organs. Ginsenoside Rg1 is an effective drug that promotes angiogenesis. Ginsenoside Rg1 composite nanoparticles were employed to induce the expression of several key epigenetic enzymes and then activate the VEGF and Notch pathways after the onset of ischemic brain lesions. We constructed nanoparticles to fully encapsulate the therapeutic drug (ginsenoside Rg1), which can be transferred into brain tissue via the receptor-mediated transfer of drug-encapsulated nanoparticles. Evaluation of the therapeutic effect of ginsenoside Rg1 complex nanovesicles (CNV) was performed by in vitro and in vivo experiments. Real-time polymerase chain reaction (RT- PCR), Western blot, immunohistochemistry staining (IHC), and Co-immunoprecipitation (co-IP) were employed to screen for epigenetic enzymes with an up-regulated expression post ginsenoside Rg1-CNV intervention. RNA sequencing, shRNA knockdown, and chromatin Immunoprecipitation (ChIP) sequencing were performed to detect the target genes of ginsenoside Rg1-CNV that regulate angiogenesis. Then, bioinformatic analysis was performed to investigate the mechanism of action of epigenetic modifying enzymes in regulating target genes. The average of the synthesized ginsenoside Rg1-CNV was 203.78±6.83 nm, the polydispersion index was 0.135±0.007, and the Zeta potential was 23.13±1.65 mV. Through in vivo and in vitro experiments, we found that it promotes the proliferation, migration, and tubular formation of brain microvascular endothelial cells (BMECs). Meanwhile, the intervention of ginsenoside Rg1-CNV promoted the demethylation of H3K27me3 within the promoter region of VEGF-A and Jagged1 genes and reduced the H3K27me3 modification within this region. The ginsenoside Rg1 nanoparticles may be an available blood-brain barrier penetrating agent for ischemic stroke.

Electrochemical Microneedles: Innovative Instruments in Health Care.

As a significant part of drug therapy, the mode of drug transport has attracted worldwide attention. Efficient drug delivery methods not only markedly improve the drug absorption rate, but also reduce the risk of infection. Recently, microneedles have combined the advantages of subcutaneous injection administration and transdermal patch administration, which is not only painless, but also has high drug absorption efficiency. In addition, microneedle-based electrochemical sensors have unique capabilities for continuous health state monitoring, playing a crucial role in the real-time monitoring of various patient physiological indicators. Therefore, they are commonly applied in both laboratories and hospitals. There are a variety of reports regarding electrochemical microneedles; however, the comprehensive introduction of new electrochemical microneedles is still rare. Herein, significant work on electrochemical microneedles over the past two years is summarized, and the main challenges faced by electrochemical microneedles and future development directions are proposed.

FORMULATION AND CHARACTERIZATION OF ODT USING DIFFERENT CO-PROCESS CONTAINING DACLATSVIR: IN VITRO AND IN VIVO PHARMACOKINETICS STUDY ON HEALTHY VOLUNTEERS FOR HEPATITIS C TREATMENT

Objective: This study aimed to prepare and evaluate oral disintegrating tablets (ODTs) of Daclatasvir dihydrochloride (DCV) using different co-processed excipients to enhance drug dissolution and improve oral bioavailability for the treatment of hepatitis C infection. Methods: Ten Daclatasvir-ODTs formulae were prepared using co-processed excipients via direct compression. The prepared formulae were evaluated according to taste masking, weight variation, thickness, friability, hardness, drug content, and wetting time. In vitro disintegration time, in vivo disintegration time, and in vitro dissolution tests were also evaluated and taken as parameters for the selection of the best formula. The selected best formula was subjected to an in vivo study on volunteers and compared to a marketed product. Results: All DCV-ODTs had acceptable physical properties in accordance with pharmacopeial standards. DCV-ODTs prepared with Pharmaburst® (F10) recorded the shortest wetting time (14±0.08s), fastest in vitro disintegration time (46±0.16s), shortest in vivo disintegration time (27±0.16s), and attained the fastest onset of dissolution (94.3±0.03 %) at 5 min to all other excipients and has been identified as the best formula. The in vivo pharmacokinetic study showed that the Pharmaburst-based formula has a significant Cmax increase of (2.17±0.28 μg/ml) compared to (1.42±0.59) for the marketed product and a significant decrease of Tmax to 60 min instead of 110 min for the marketed product. Conclusion: The in vivo pharmacokinetic study in humans showed that the ODTs was found to be appropriate for delivery of Daclatasvir with a faster drug absorption rate when compared to the marketed products with applicable taste related to the nature of dosage form.

Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery.

The oral route is the most common and practical means of drug administration, particularly from a patient’s perspective. However, the pharmacokinetic profile of oral drugs depends on the rate of drug absorption through the intestinal wall before entering the systemic circulation. However, the enteric epithelium represents one of the major limiting steps for drug absorption, due to the presence of efflux transporters on the intestinal membrane, mucous layer, enzymatic degradation, and the existence of tight junctions along the intestinal linings. These challenges are more noticeable for hydrophilic drugs, high molecular weight drugs, and drugs that are substrates of the efflux transporters. Another challenge faced by oral drug delivery is the presence of first-pass hepatic metabolism that can result in reduced drug bioavailability. Over the years, a wide range of compounds have been investigated for their permeation-enhancing effect in order to circumvent these challenges. There is also a growing interest in developing nanocarrier-based formulation strategies to enhance the drug absorption. Therefore, this review aims to provide an overview of the challenges faced by oral drug delivery and selected strategies to enhance the oral drug absorption, including the application of absorption enhancers and nanocarrier-based formulations based on in vitro, in vivo, and in situ studies.

Herbosomes: A Potent drug carrier

Herbal medications have a wide range of phytochemical ingredients, the majority of which are flavonoids and terpenoids, which have a vivid range of applications. The use of polar phyto-constituents is restricted due to their poor absorption and bioavailability. Poor bioavailability can be overcome by developing a suitable drug delivery system, such as the herbosome (Phospholipids) based drug delivery system, which has been found to be promising for better and more effective drug delivery and can increase the rate and extent of drug absorption across the lipoidal bio-film. Herbosome is one of the phospholipid-based herbal drug delivery systems with a higher absorption and stability profile than the others. The herbosome has the potential to play a critical role in the value delivery of Phyto-constituents like flavonoids, and vitamin E. Herbosomes have a wide range of applications aside from homegrown diets and beauty care products. As a result of their medicinal use, several locations of herbosomes will be discovered in the future.

Effects of salinity on the absorption and elimination of residues of the fungicide ridomil in Procambarus clarkii (Girard, 1852) (Decapoda: Astacidea: Cambaridae)

Abstract We explored the pharmacokinetics of the antimicrobial agent ridomil in the crayfish Procambarus clarkii (Girard, 1852) under different salinity conditions. The concentration of ridomil in hemolymph, liver, and muscle of individuals soaked in ridomil in fresh water and brackish water with a salinity of 3‰ was determined by high-performance liquid chromatography. Hemolymph was in line with the first-order absorption, two-compartment open model, and the liver and muscles were in line with the first-order absorption, one-compartment open model. The maximum concentration(Cmax) in the hemolymph in fresh and brackish-water groups were 296 mg l–1 and 452 mg l–1, respectively. The maximum time (Tmax) of hemolymph in the fresh and brackish-water groups were 8h and 24h, respectively. The Cmax in liver and muscle in the freshwater group were 4,125 mg l–1 and 2,702 mg l–1, respectively, and 2,362 mg l–1 and 2,274 mg l–1, respectively, in the brackish-water group. The Tmax of liver and muscle in the freshwater group were 0.25 h and 18 h, respectively, 36 h and 24 h, respectively, in the brackish-water group. Results indicate that the concentration of ridomil in the hemolymph was lower in the freshwater group than that in the brackish-water group, but the concentration in liver and muscle tissues in the freshwater group was higher than that in the brackish-water group. Salinity can therefore affect the drug absorption rate of ridomil in the hemolymph of Procambarus clarkii.

Drug delivery with therapeutic lens for the glaucoma treatment in the anterior eye chamber: a numerical simulation

One of these diseases, known as cataracts, is frequently treated with topical medications such as eye drops that pass through the eye's anterior chamber (AC). Unfortunately, the effect is critically reduced due to the short presence of the drug in the eye (approximately 30 s). However, one of the best practices to treat the problem is to use contact lenses that carry the drug, which causes the drug to be released with a smaller amount and longer duration (Approx. 30 min). Therefore, this study aims to investigate the rate of drug absorption in the eye through contact lenses. For the numerical simulation in this paper, a total of four layers are considered, namely the lens, inner tears, cornea, and aura. The drug contact lens is modeled as a source of drug release, and at the end, the drug concentration in the corneal layer and the anterior chamber (AC) and the peak release time of the drug concentration are measured. The results demonstrate that the amount of drug in the lens decreases over time. Therefore, this study aims to investigate the rate of drug absorption in the eye through contact lenses.

Low Drug Loading Hampers the Clinical Translation of Peptide Drugs-Containing Metered-Dose Inhalers.

Peptide-based drugs have attracted extensive attention from the medical and pharmaceutical industry because of their relatively high safety and efficacy. However, most of the peptide drugs approved are administrated by injection, which can easily cause poor patient compliance. In this circumstance, pulmonary administration as an alternative to injection administration can not only avoid the above issue but also accelerate the absorption rate of peptide drugs and improve bioavailability. Among the pulmonary delivery systems available on the market, metered-dose inhalers (MDIs) have emerged as appealing candidates for pulmonary delivery systems with clinical translational value, owing to their many merits, including portable, easy-to-operate, and cost-effective properties. Nevertheless, the industrialization of peptide drugs-containing MDIs encounters a bottleneck of low drug loading, owing to the incompatibility between the propellant and the peptide drugs, which cannot be effectively overcome by the current carrier particle encapsulation strategy. Herein, we put forward the following strategies: (1) To screen amphiphilic materials with high surface activity and strong interaction with peptide drugs; (2) To construct a chemical connection between peptide drugs and amphiphilic substances; (3) To optimize the cosolvent for dispersing peptide drugs. We suppose these strategies have the potential to defeat the bottleneck problem and provide a new idea for the industrialization of peptide drugs-containing MDIs.

Prediction of Oral Drug Absorption in Rats from In Vitro Data.

In drug discovery, rats are widely used for pharmacological and toxicological studies. We previously reported that a mechanism-based oral absorption model, the gastrointestinal unified theoretical framework (GUT framework), can appropriately predict the fraction of a dose absorbed (Fa) in humans and dogs. However, there are large species differences between humans and rats. The purpose of the present study was to evaluate the predictability of the GUT framework for rat Fa. The Fa values of 20 model drugs (a total of 39 Fa data) were predicted in a bottom-up manner. Based on the literature survey, the bile acid concentration (Cbile) and the intestinal fluid volume were set to 15mM and 4mL/kg, respectively, five and two times higher than in humans. LogP, pKa, molecular weight, intrinsic solubility, bile micelle partition coefficients, and Caco-2 permeability were used as input data. The Fa values were appropriately predicted for highly soluble drugs (absolute average fold error (AAFE) = 1.65, 18 Fa data) and poorly soluble drugs (AAFE = 1.57, 21 Fa data). When the species difference in Cbile was ignored, Fa was over- and under-predicted for permeability and solubility limited cases, respectively. High Cbile in rats reduces the free fraction of drug molecules available for epithelial membrane permeation while increasing the solubility of poorly soluble drugs. The Fa values in rats were appropriately predicted by the GUT framework. This result would be of great help for a better understanding of species differences and model-informed preclinical formulation development.