Maintain Drug Levels Research Articles

Prolonged and Regulated Drug Delivery Mechanisms

Prolonged and regulated drug delivery mechanisms (PRDDM) have transformed pharmacotherapy by improving therapeutic effectiveness while reducing adverse effects. These advanced formulations are specifically designed to dispense active pharmaceutical ingredients at a controlled rate, ensuring a lasting therapeutic effect and maintaining drug levels within the optimal therapeutic range. Prolonged release mechanisms are developed to administer medication consistently over a prolonged duration, minimizing the need for frequent dosing and enhancing adherence to treat. On other hand, prolonged release mechanism (PRM) systems deliver a more accurate and consistent release profile, facilitating personalized drug administration according to individual patient requirements. To achieve PRDDM, various strategies are employed, including the incorporation of biodegradable polymers, hydrogels, and osmotic systems. The formulation elements can be customized to regulate drug release rates using processes like diffusion, breakdown/ osmotic. Additionally, progress in nanotechnology and 3D printing has opened new avenues for developing innovative drug delivery mechanisms.However, despite the many benefits, challenges like formulation stability, scalability manufacturing, and regulatory compliance remain significant issues that require attention. In summary, PRDDM signify notable progress in contemporary medicine, leading to better patient outcomes and enhanced therapeutic strategies. Ongoing research and innovation in this area are crucial to addressing current challenges and unlocking the full potential of cutting-edge drug delivery mechanisms.

Preparation, characterization, and liver targeting evaluation of a novel sustained-release brucine self-assembled micelle mediated by glycyrrhetinic acid.

Background: Cancer is a serious threat to human life, health and social development. In recent years, nanomicelles, as an emerging drug carrier material, have gradually entered people's field of vision because of their advantages of improving bioavailability, maintaining drug levels, reducing systemic side effects and increasing drug accumulation at target sites. Methods: In this study, B-GPSG nano-micelles were prepared by film dispersion hydration method using brucine as model drug and glycyrrhetinic acid-polyethylene glycol-3-methylene glycol-dithiodipropionic acid-glycerol monostearate polymer as nano-carrier. The preparation process, characterization, drug release in vitro, pharmacokinetics and liver targeting were investigated. Results: The results showed that the range of particle size, polydispersion index and Zeta potential were 102.7 ± 1.09nm, 0.201 ± 0.02 and -24.5 ± 0.19mV respectively. The entrapment efficiency and drug loading were 83.79 ± 2.13% and 12.56 ± 0.09%, respectively. The drug release experiments in vitro and pharmacokinetic experiments showed that it had obvious sustained release effect. For pharmacokinetics study, it shows that both the B-GPSG solution group and the B-PSG solution group changed the metabolic kinetic parameters of brucine, but the B-GPSG solution group had a better effect. Compared with the B-PSG solution group, the drug was more prolonged in rats. The half-life in the body and the retention time in the body of B-GPSG are more helpful to improve the bioavailability of the drug and play a long-term effect. The tail vein injection results of mice indicate that B-GPSG can target and accumulate brucine in the liver without affecting other key organs. Cell uptake experiments and tissue distribution experiments in vivo show that glycyrrhetinic acid modified nano-micelles can increase the accumulation of brucine in hepatocytes, has a good liver targeting effect, and can be used as a new preparation for the treatment of liver cancer. Conclusion: The B-SPSG prepared in this experiment can provide a new treatment method and research idea for the treatment of liver cancer.

Kajian Penggunaan Matriks Pada Formulasi Tablet Lepas Lambat

This research discusses the use of matrices in sustained-release tablet formulations to optimize the active substance release profile. Extended-release tablets are a type of tablet formulation designed to release the active substance gradually in the body over a certain period of time. The main purpose of sustained-release tablets is to maintain drug levels in the blood or target area over a longer period of time, compared to conventional tablets which release the active substance quickly after ingestion. The method used in this research is a qualitative approach which aims to deepen an in-depth understanding of the phenomenon being studied. As a result, selecting the right type of matrix proves to be crucial in achieving the expected therapeutic effectiveness. Polymer matrices, both natural and synthetic, play an important role in controlling the stability and efficiency of tablets and their ability to gradually release active substances.

Novel nano-in-micro fabrication technique of diclofenac nanoparticles loaded microneedle patches for localised and systemic drug delivery

Diclofenac, a nonsteroidal anti-inflammatory drug, is commonly prescribed for managing osteoarthritis, rheumatoid arthritis, and post-surgical pain. However, oral administration of diclofenac often leads to adverse effects. This study introduces an innovative nano-in-micro approach to create diclofenac nanoparticle-loaded microneedle patches aimed at localised, sustained pain relief, circumventing the drawbacks of oral delivery. The nanoparticles were produced via wet-milling, achieving an average size of 200nm, and then incorporated into microneedle patches. These patches showed improved skin penetration in ex vivo tests using Franz-cell setups compared to traditional diclofenac formulations. In vivo tests on rats revealed that the nanoparticle-loaded microneedle patches allowed for quick drug uptake and prolonged release, maintaining drug levels in tissues for up to 72h. With a systemic bioavailability of 57%, these patches prove to be an effective means of transdermal drug delivery. This study highlights the potential of this novel microneedle delivery system in enhancing the treatment of chronic pain with reduced systemic side effects.

A Review on Ocular Drug Delivery System

The major challenge faced by today’s pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. KEYWORDS: Cornea; Emulsions; Implants; Liposome; Nanomicelles;

Development and validation of an LC-MS/MS method for ruxolitinib quantification: advancing personalized therapy in hematologic malignancies.

Hematologic malignancies such as leukemia and lymphoma present treatment challenges due to their genetic and molecular heterogeneity. Ruxolitinib, a Janus kinase (JAK) inhibitor, has demonstrated efficacy in managing these cancers. However, optimal therapeutic outcomes are contingent upon maintaining drug levels within a therapeutic window, highlighting the necessity for precise drug monitoring. We developed a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to quantify ruxolitinib in human plasma, improving upon traditional methods in specificity, sensitivity, and efficiency. The process involved the use of advanced chromatographic techniques and robust mass spectrometric conditions to ensure high accuracy and minimal matrix effects. The study was conducted using samples from 20 patients undergoing treatment, with calibration standards ranging from 10 to 2000ng/mL. The method displayed linearity (R 2 > 0.99) across the studied range and proved highly selective with no significant interference observed. The method's precision and accuracy met FDA guidelines, with recovery rates consistently exceeding 85%. Clinical application demonstrated significant variability in ruxolitinib plasma levels among patients, reinforcing the need for individualized dosing schedules. The validated LC-MS/MS method offers a reliable and efficient tool for the therapeutic drug monitoring of ruxolitinib, facilitating personalized treatment approaches in hematologic malignancies. This approach promises to enhance patient outcomes by optimizing dosing to reduce toxicity and improve efficacy.

OCULAR DRUG DELIVERY SYSTEMS: AN OVERVIEW

The treatment for the ophthalmic diseases are topical route because of the various ocular barrier. Ocular drug delivery systems are considered as major challenges by today’s pharmacologist and formulation scientist. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery techniques, which may surpass these barriers and maintain drug levels in tissues. There are many eye ailments which affected to eye and one can loss the eye sight also. Therefore, many ophthalmic drug delivery systems are available. These are classified as conventional and non- conventional (newer) drug delivery systems. Most commonly available ophthalmic preparations are eye drops and ointments about 70% of the eye dosage formulations in market. So overcome to these problems newer pharmaceutical ophthalmic formulation such as in-situ gel, nanoparticle, liposome, nanosuspension, microemulsion, intophoresis and ocular inserts have been developed in last three decades increase the bioavailability of the drug as a sustained and controlled manner.

Chronic limbic epilepsy models for therapy discovery: Protocols to improve efficiency.

There have been recommendations to improve therapy discovery for epilepsy by incorporating chronic epilepsy models into the preclinical process, but unpredictable seizures and difficulties in maintaining drug levels over prolonged periods have been obstacles to using these animals. We report new protocols in which drugs are administered through a new chronic gastric tube to rats with higher seizure frequencies to minimize these obstacles. Adult rats with spontaneous limbic seizures following an episode of limbic status epilepticus induced by electrical hippocampal stimulation were monitored with long-term video- electroencephalography (EEG). Animals with a predetermined baseline seizure frequency received an intragastric tube for drug administration. Carbamazepine, levetiracetam, phenobarbital, and phenytoin were tested with either an acute protocol (an increasing single dose every other day for a maximum of three doses) or with a chronic protocol (multiple administrations of one dose for a week). Drug levels were obtained to correlate the effect with the level. With the acute protocol, all four drugs induced a clear dose-related response. Similar dose-related responses were seen following the week-long dosing protocol for carbamazepine, phenobarbital, and phenytoin, and these responses were associated with drug levels that were in the human therapeutic range. The response to chronic levetiracetam was much less robust. The gastric tube route of administration was well tolerated over a number of months. Using rats with stable, higher seizure frequencies made it possible to identify the potential of a drug to suppress seizures in a realistic model of epilepsy with drug levels that are similar to those of human therapeutic levels. The acute protocol provided a full dose response in 1 week. The chronic administration protocol further differentiated drugs that may be effective long term. The gastric tube facilitates a less stressful, humane, and consistent administration of multiple doses.

Combining Clinical and Genetic Factors to Predict Tacrolimus Levels in Pediatric Solid Organ Transplants: Problem Solved?

Combining Clinical and Genetic Factors to Predict Tacrolimus Levels in Pediatric Solid Organ Transplants: Problem Solved?

Development and in vitro evaluation of chitosan based system for local delivery of atorvastatin for treatment of periodontitis

In recent years, statin group drugs have been widely investigated in treatment of periodontal diseases due to their anti-inflammatory effect. The efficacy of statins can be enhanced by local administration into the periodontal pocket by appropriate delivery systems. The aim of our study was to develop a bioadhesive delivery system for local delivery of atorvastatin in treatment of periodontal disease. For this purpose, gel formulations were prepared using different types of chitosan (base and water soluble) and viscosity, bioadhesivity and syringeability of the gels as well as in vitro drug release properties were investigated vitro. Furthermore, anti-inflammatory effect of the formulations was studied in vitro using tumor necrosis factor (TNF)-alfa induced human gingival fibroblast (hGF) cells. Release of proinflammatory (IL-1β, IL-6, IL-8) and anti-inflammatory (TGF-β1, TGF-β2, TGF-β3, IL-10) cytokines were measured after incubating the hGF cells with the formulations. The viscosity of the formulations was found to be suitable for a local application into periodontal pocket. In presence of drug, bioadhesive property of the formulations was found to increase, and bioadhesion force was within the range, which would retain the delivery system at the application site, subsequently maintain drug levels at desired amount for longer period of time. The release of atorvastatin from the gels was found to be slower than that of the solution. The cytokine levels were found to decrease following application of the formulations, and anti-inflammatory effect was observed to enhance in presence of chitosan. No significant differences were found between base and water-soluble chitosan.

Therapeutic Drug Monitoring of Levetiracetam in Select Populations.

Levetiracetam (LEV) is a broad spectrum antiepileptic drug (AED) that has a more favorable side effect profile compared to older AEDs. Therapeutic drug monitoring (TDM) of LEV is generally unnecessary given its linear and predictable dose-serum concentration relationship, lack of drug-drug interactions, and broad therapeutic window. However, there is growing evidence showing that alteration of LEV pharmacokinetics (PK) may occur in special populations calling for the need for TDM. The purpose of this review was to summarize current literature surrounding altered LEV PK in special patient populations and determine if there is a need for levetiracetam TDM. A literature search of MEDLINE (1946 - November 2017) database of available evidence pertaining to altered LEV PK in humans was conducted. A total of 51 articles were found. There has not been a positive correlation shown between LEV levels and efficacy or toxicity. Variable LEV levels are reported in the literature with respect to adverse effects, seizures and efficacy occurring below, within and above the supposed reference ranges. Age is a major contributor to altered pharmacokinetics of LEV as shown in elderly patients and pediatric patients. Compared to adults, clearance of LEV has been shown to be decreased by almost half in patients over 65 and increased by 30-40% in pediatric patients. LEV pharmacokinetics varied further when data from its use in neonates was explored. LEV clearance declined in a linear fashion with declining estimates of creatinine clearance but was variable in patients with end-stage renal failure or those requiring renal replacement therapy. In patients who were critically ill, LEV clearance may be augmented and these patients may require higher doses of medications to maintain drug levels. In patients who are pregnant, LEV levels are likely to decline as pregnancy progresses due to changes in glomerular filtration rate and remain variable in the post-partum period. Routine TDM of levetiracetam is not recommended for all populations, however, it may be beneficial to maintain an individual therapeutic range in patients where the PK of LEV may be altered, such as in patients who are critically ill patients, pregnant, pediatrics or elderly.

A Nanoscale Tool for Photoacoustic-Based Measurements of Clotting Time and Therapeutic Drug Monitoring of Heparin.

Heparin anticoagulation therapy is an indispensable feature of clinical care yet has a narrow therapeutic window and is the second most common intensive care unit (ICU) medication error. The active partial thromboplastin time (aPTT) monitors heparin but suffers from long turnaround times, a variable reference range, limited utility with low molecular weight heparin, and poor correlation to dose. Here, we describe a photoacoustic imaging technique to monitor heparin concentration using methylene blue as a simple and Federal Drug Administration-approved contrast agent. We found a strong correlation between heparin concentration and photoacoustic signal measured in phosphate buffered saline (PBS) and blood. Clinically relevant heparin concentrations were detected in blood in 32 s with a detection limit of 0.28 U/mL. We validated this imaging approach by correlation to the aPTT (Pearson's r = 0.86; p < 0.05) as well as with protamine sulfate treatment. This technique also has good utility with low molecular weight heparin (enoxaparin) including a blood detection limit of 72 μg/mL. We then used these findings to create a nanoparticle-based hybrid material that can immobilize methylene blue for potential applications as a wearable/implantable heparin sensor to maintain drug levels in the therapeutic window. To the best of our knowledge, this is the first use of photoacoustics to image anticoagulation therapy with significant potential implications to the cardiovascular and surgical community.

The Clinical Significance of Voriconazole Therapeutic Drug Monitoring in Children With Invasive Fungal Infections

Voriconazole is an antifungal drug used to treat fungal infections. This was a retrospective study of 61 children with hemato-oncologic diseases or solid organ transplantation who were administered voriconazole for invasive fungal infections. Of the 61 patients, 31 (50.8%) were in the therapeutic drug monitoring (TDM) group, and 30 (49.2%) were in the non-TDM group. At 12 weeks, treatment failure rate in the non-TDM group was higher than the TDM group (78.6% versus 40.0%, p = 0.038). Drug discontinuation due to adverse events was less frequent in the TDM group than the non-TDM group (26.0% versus 92.3%, p = 0.001). Children required higher dosages to maintain drug levels within the targeted therapeutic range: an average of 8.3 mg/kg/dose in patients <12 years old and 6.9 mg/kg/dose for those ≥12 years old. Treatment failure rates were higher in patients whose voriconazole levels remained below 1.0 mg/L for more than 50% of their treatment duration than those above 1.0 mg/L (71.4% vs. 9.1% after 12 weeks, p = 0.013). Serial monitoring of voriconazole levels in children is important for improving treatment response and preventing unnecessary drug discontinuation. Higher dosages are needed in children to reach therapeutic range.

Defining success with HIV pre-exposure prophylaxis: a prevention-effective adherence paradigm.

Clinical trial data have shown that oral pre-exposure prophylaxis (PrEP) is efficacious when taken as prescribed; however, PrEP adherence is complex and must be understood within the context of variable risk for HIV infection and use of other HIV prevention methods. Different levels of adherence may be needed in different populations to achieve HIV prevention, and the optimal methods for achieving the necessary adherence for both individual and public health benefits are unknown. Guidance for PrEP use must consider these questions to determine the success of PrEP-based HIV prevention programs. In this article, we propose a new paradigm for understanding and measuring PrEP adherence, termed prevention-effective adherence, which incorporates dynamic HIV acquisition risk behaviors and the use of HIV alternative prevention strategies. We discuss the need for daily PrEP use only during periods of risk for HIV exposure, describe key issues for measuring and understanding relevant behaviors, review lessons from another health prevention field (i.e., family planning), and provide guidance for prevention-effective PrEP use. Moreover, we challenge emerging calls for sustained, near perfect PrEP adherence regardless of risk exposure and offer a more practical and public health-focused vision for this prevention intervention.

A comparative study on long-term MTX controlled release from intercalated nanocomposites for nanomedicine applications

The feasibility of some mesoporous materials such as SBA-15 and MCM-41 silica, LDH (layered double hydroxide) (Mg3Al-NO3) and MC (mesoporous carbon) have been comparatively evaluated for oral drug delivery applications, in order to broaden the range of matrices and implicitly to develop the class of drug delivery systems based on diffusion mechanism. As well known, methotrexate (MTX) is used widely to treat various neoplastic diseases such as acute lymphoblast leukemia, lymphoma and solid cancers and autoimmune diseases such as psoriasis and rheumatoid arthritis. The commercially available formulations of this drug have disadvantages due to the traditional release process that occurs in the body. Thus, this work is focused on the long-term controlled MTX delivery because this one could eliminate over or underdosing, could maintain drug levels in desired range, could increase patient compliance and prevent the side effects. Therefore, the mesoporous materials are used and efficient MTX-delivery systems, based on above-mentioned mesoporous materials, are successfully prepared by intercalation. The obtained drug carriers were tested in the controlled MTX-drug release process and the influence of the pore morphology and geometry on MTX release profiles was extensively studied comparatively. The prepared MTX delivery systems were characterized by FTIR and UV-vis spectroscopy, N2 sorption measurements. Then, the data obtained from the in vitro release studies have been analyzed, and in order to evaluate the MTX-release mechanism and kinetics, the Korsmeyer-Peppas equation has been applied.

Ocular drug delivery systems: An overview.

The major challenge faced by today's pharmacologist and formulation scientist is ocular drug delivery. Topical eye drop is the most convenient and patient compliant route of drug administration, especially for the treatment of anterior segment diseases. Delivery of drugs to the targeted ocular tissues is restricted by various precorneal, dynamic and static ocular barriers. Also, therapeutic drug levels are not maintained for longer duration in target tissues. In the past two decades, ocular drug delivery research acceleratedly advanced towards developing a novel, safe and patient compliant formulation and drug delivery devices/techniques, which may surpass these barriers and maintain drug levels in tissues. Anterior segment drug delivery advances are witnessed by modulation of conventional topical solutions with permeation and viscosity enhancers. Also, it includes development of conventional topical formulations such as suspensions, emulsions and ointments. Various nanoformulations have also been introduced for anterior segment ocular drug delivery. On the other hand, for posterior ocular delivery, research has been immensely focused towards development of drug releasing devices and nanoformulations for treating chronic vitreoretinal diseases. These novel devices and/or formulations may help to surpass ocular barriers and associated side effects with conventional topical drops. Also, these novel devices and/or formulations are easy to formulate, no/negligibly irritating, possess high precorneal residence time, sustain the drug release, and enhance ocular bioavailability of therapeutics. An update of current research advancement in ocular drug delivery necessitates and helps drug delivery scientists to modulate their think process and develop novel and safe drug delivery strategies. Current review intends to summarize the existing conventional formulations for ocular delivery and their advancements followed by current nanotechnology based formulation developments. Also, recent developments with other ocular drug delivery strategies employing in situ gels, implants, contact lens and microneedles have been discussed.

Postoperative Transplant Immunosuppression in the Critical Care Unit

Postoperative Transplant Immunosuppression in the Critical Care Unit

Lipid-Based Nanocarriers for CNS-Targeted Drug Delivery

Nanotechnology exerts an increasing impact on the development of more effective tools for the diagnosis and treatment of human diseases. This applies in particular to central nervous system (CNS) disorders. Development of therapeutics for CNS is, in fact, one of the most challenging areas in drug development, mainly due to the presence of the blood-brain barrier (BBB) which separates the blood from the cerebral parenchyma thus limiting the brain uptake of the vast majority of neurotherapeutic agents. Among the several strategies which have been developed over the last years in order to overcome this problem, nanotechnology-based approaches have gained increasing attention as the most promising strategies for CNS targeted drug delivery. Nanocarriers offer several advantages such as the possibility to maintain drug levels in a therapeutically desirable range, as well as the increase of half-lives, solubility, stability and permeability of drugs. Furthermore, the system can be designed in such a way as to release the drug in a controlled way or in a triggered way. This review focuses on lipid-based nanocarriers and more specifically on liposomes, lipid-core micelles, and lipid nanocapsules, and provides an update on their composition and use, including recent patents in the field.

The Motivation to Self-Administer is Increased After a History of Spiking Brain Levels of Cocaine

Recent attempts to model the addiction process in rodents have focused on cocaine self-administration procedures that provide extended daily access. Such procedures produce a characteristic loading phase during which blood levels rapidly rise and then are maintained within an elevated range for the duration of the session. The present experiments tested the hypothesis that multiple fast-rising spikes in cocaine levels contribute to the addiction process more robustly than constant, maintained drug levels. Here, we compared the effects of various cocaine self-administration procedures that produced very different patterns of drug intake and drug dynamics on Pmax, a behavioral economic measure of the motivation to self-administer drug. Two groups received intermittent access (IntA) to cocaine during daily 6-h sessions. Access was limited to twelve 5-min trials that alternated with 25-min timeout periods, using either a hold-down procedure or a fixed ratio 1 (FR1). Cocaine levels could not be maintained with this procedure; instead the animals experienced 12 fast-rising spikes in cocaine levels each day. The IntA groups were compared with groups given 6-h FR1 long access and 2-h short access sessions and two other control groups. Here, we report that cocaine self-administration procedures resulting in repeatedly spiking drug levels produce more robust increases in Pmax than procedures resulting in maintained high levels of cocaine. These results suggest that rapid spiking of brain-cocaine levels is sufficient to increase the motivation to self-administer cocaine.

Evidence for learned skill during cocaine self-administration in rats

It has been proposed that cocaine abuse results in skilled or "automatic" drug-taking behaviors. Brain regions important for skill learning are implicated in cocaine self-administration. However, the development of skill during self-administration has not been investigated. The present experiment investigated the development of skilled self-administration over extended drug use by employing a novel operant vertical head movement under discriminative stimulus (S(D)) control. In addition, the capacity of the head movement to serve as an operant was tested by manipulating drug levels above or below satiety drug levels via frequent noncontingent microinfusions (0.2 s) of cocaine. Animals acquired the vertical head movement operant, which increased in number over days. Task learning was demonstrated by reduced reaction time in response to the S(D), increased propensity to self-administer upon S(D) presentation, and escalated drug consumption over days. Skill learning was demonstrated by (1) an increase over days in the velocity of operant movements, as a function of shorter duration but not altered distance, and (2) an increase over days in the probability of initiating the operant at the optimal starting position. Evidence that responding was specific to self-administration was revealed during periods of experimenter-manipulated drug level: maintaining drug levels above satiety decreased responding while maintaining drug levels below satiety increased responding. Under the specific set of circumstances tested herein, cocaine self-administration became skilled over extended drug use. The vertical head movement can be used as an operant comparable to lever pressing with the additional benefit of quantifying skill learning.