Route For Systemic Drug Delivery Research Articles

Inhaled fentanyl aerosol through a drug-device combination for breakthrough cancer pain: A multicenter, randomized, double-blind, placebo-controlled trial.

e24058 Background: Breakthrough cancer pain (BTcP) can significantly impact the life quality of the cancer patient. Wide-used rapid-onset opioids (ROOs) for BTcP are transmucosal fentanyl-based preparations. Inhaled fentanyl demonstrated similar pharmacokinetic properties as intravenous administration in healthy volunteers. Fentanyl aerosol can be generated via hand-held drug-device delivery system, providing rapid, consistent multi-dose administration. Fentanyl inhalant was explored as alternative treatment of BTcP in cancer patients in this study to evaluate its efficacy, safety, and tolerability in BTcP patients with well-controlled background cancer pain. Methods: Adults ≥18 years with cancer are eligible if they were experiencing persistent cancer- or treatment-related pain with above mild severity and 1-4 episode occurrences daily. Each patient was treated and observed for 6 BTcP episodes (4 with fentanyl inhalant, 2 with placebo). During each episode, patients were allowed to inhale up to six shots within 1 hour. Pain intensity was recorded using 11-point Numerical Rating Scale (NRS) at predefined time points. The primary endpoint was the time-weighted Sum of Pain Intensity Difference scores at 30 minutes (SPID30) after the first inhalation. Results: 335 BTcP episodes in 59 patients were treated. SPID30 was analyzed using mixed model of repeated measures with treatment (fentanyl inhalant or placebo), BTcP episode, baseline pain intensity score as fixed factors, and subject as random factor. Mean SPID30 ± SD was -97.4 ± 48.43 for fentanyl-treated episodes, and -64.6 ± 40.25 for placebo-treated episodes. Based on treatment adjustment in the mixed covariance model, significant difference (p < 0.001) was reported with mean treatment difference of -27.7 (LS-mean ± SD, -94.2 ± 4.49 for fentanyl and -66.5 ± 4.86 for placebo). It enlarged at 60 minutes (SPID60) with a mean treatment difference of -57.9 (LS-mean ± SD, -231.4 ±105.14 for fentanyl and -162.2 ± 91.21 for placebo, p < 0.001). Significant differences in PID for episodes treated with fentanyl versus placebo were seen 4 minutes after the first dosing and maintained up to 60 minutes. Other endpoints showed statistical significance favoring fentanyl treatment, including the proportion of NRS ≤ 3, NRS pain scores decreased ≥ 33% or ≥ 50% from baseline after completion of BTcP treatment within 30 minutes of first dose, and Pain Relief Score Within 30 Minutes of the First Dose (PR30). Only 4.4% of BTcP episodes required rescue medication in fentanyl group. Major adverse events were mild or moderate in severity and were typical for opioid drugs. Conclusions: Fentanyl inhalant is safe, effective, and well-tolerated for managing BTcP. It provides a non-invasive route for systemic drug delivery and can be self-administered or given by family caregivers as personalized and regular pain management. Clinical trial information: NCT05531422 .

Buccal Patches: A Comprehensive review

The buccal mucosa is one of the administration sites that might provide an alternative for peroral administration. The successful delivery of drugs across the oral mucosa represents a continuing challenge, as well as a great opportunity. Buccal delivery, has progressed far beyond the use of traditional dosage forms with novel approaches emerging continuously. Buccal drug delivery system in which drug enters directly in systemic circulation thereby by passing the first pass effect. This is painless and without discomfort, precise dosage form and facilitates ease of removal without significant associated pain. Moreover it shows better stability, patient compliance; uniform and sustained drug release and above all easy and cheap methods of preparation which can be done with various commonly available biocompatible polymers. The buccal route has been researched for a wide variety of drugs and has gained significant attention and momentum since it offers remarkable advantages. Over past few decades, buccal route for systemic drug delivery using mucoadhesive polymers to significantly improve the performance of many drugs has been of profound interest. Present article deals with the different aspect of the buccal patches.

Optimization of Spray Drying Process Parameters for the Preparation of Inhalable Mannitol-Based Microparticles Using a Box-Behnken Experimental Design.

Inhalation is used for local therapy of the lungs and as an alternative route for systemic drug delivery. Modern powder inhalation systems try to target the required site of action/absorption in the respiratory tract. Large porous particles (LPPs) with a size >5 μm and a low mass density (usually measured as bulk or tapped) of <0.4 g/cm3 can avoid protective lung mechanisms. Their suitable aerodynamic properties make them perspective formulations for deep lung deposition. This experiment studied the effect of spray-drying process parameters on LPP properties. An experimental design of twelve experiments with a central point was realized using the Box-Behnken method. Three process parameters (drying temperature, pump speed, and air speed) were combined on three levels. Particles were formed from a D-mannitol solution, representing a perspective material for lung microparticles. The microparticles were characterized in terms of physical size (laser diffraction), aerodynamic diameter (aerodynamic particle sizer), morphology (SEM), and densities. The novelty and main goal of this research were to describe how the complex parameters of the spray-drying process affect the properties of mannitol LPPs. New findings can provide valuable data to other researchers, leading to the easy tuning of the properties of spray-dried particles by changing the process setup.

Factors Affecting Drug Exposure after Inhalation.

Administration of drugs by inhalation is mainly used to treat lung diseases and is being investigated as a possible route for systemic drug delivery. It offers several benefits, but it is also fraught with many difficulties. The lung is a complex organ with complicated physiology and specific pharmacokinetic processes. Therefore, the exposure and subsequently efficacy of a drug after inhalation is affected by a number of factors. In this review, we summarize the main variables that may affect drug fate after inhalation delivery, such as physicochemical properties of the drug, pulmonary clearance and metabolism, pathophysiological factors and inhalation device. Factors that have impact on pharmacokinetic processes need to be considered during development as their correct setting can lead to new effective inhaled drugs.

FORMULATION AND EVALUATION OF CLOPIDOGREL BISULFATE TRANSDERMAL PATCHES

Transdermal drug delivery is an alternative route for systemic drug delivery which minimizes the absorption and increases the bioavailability. The main objective of the present work was to develop a suitable matrix type transdermal drug delivery system of Clopidogrel bisulphate using different polymers HPMC E15, Eudragit L100 and to compare the drug release through physical method and chemical method. Matrix type transdermal patches containing Clopidogrel Bisulfate were prepared by solvent evaporation technique. The prepared transdermal patches were evaluated for Thickness, folding endurance, tensile strength and in vitro studies. The prepared transdermal drug delivery system of Clopidogrel bisulphate using different polymers such as HPMC E15 and Eudragit L 100 had shown good promising results for all the evaluated parameters. Based on the In-vitro drug release, drug content and folding endurance results formulation F4 was concluded as an optimized formulation which shows its higher percentage of drug release.&#x0D; Keywords: Transdermal drug delivery, Clopidogrel bisulphate, HPMC E15, Eudragit L100

Formulation Design of Hydrocortisone Films for the Treatment of Aphthous Ulcers.

Research and development in oral drug delivery has evolved to the changeover of solid dosage forms from tablets to oral films. These films offer an elegant route for systemic drug delivery, with an advantage for patients who are suffering from difficulty in swallowing larger oral dosage forms. Aphthous ulcers are the most common oral lesions and are round or oval, with a grayish yellow, crateriform base. For the treatment of aphthous ulcers various marketed product are available, such as vitamin B12 tablets, benzydamine hydrochloride mouthwash or spray, steroid lozenges, and local anesthetics. Hence hydrocortisone is selected as the drug of choice for the treatment of aphthous ulcers, exhibiting anti-inflammatory and immunosuppressant properties that inhibit the clinical manifestations. The main aim of the present study was to develop a hydrocortisone film in order to improve the therapeutic efficacy and bioavailability of hydrocortisone for the treatment of aphthous ulcers. The hydrocortisone film was developed containing various concentrations of methylcellulose and propylene glycol (1.0-2.0% w/v) by solvent casting. The prepared films were evaluated for various characterization studies like film forming capacity, visual appearance, thickness, weight variation, folding endurance, surface pH, drug content, disintegration time, tensile strength, in vitro release study, ex vivo study, and stability studies. A total of five formulations were developed, out of which formulation F2 (1.25% w/v) is considered the optimized formulation as it showed the best results with respect to all characterization studies. A disintegration time of 44 s and maximum in vitro drug release, i.e. 97.55%, were observed. Further, no significant changes were observed during stability studies for the optimized formulation. Hydrocortisone oral films can be formulated as a potentially useful tool for effective treatment of aphthous ulcers with improved bioavailability, rapid onset of action, and increased patient compliance.

Sublingual route for systemic drug delivery

Drug delivery via the oral mucous membrane is considered to be a promising alternative to the oral route. Sublingual route is a rapid onset of action and better patient compliance than orally ingested tablets. Sublingual literally meaning is “under the tongue”, administrating substance via mouth in such a way that the substance is rapidly absorbed via blood vessels under tongue. The portion of drug absorbed through the sublingual blood vessels bypasses the hepatic first‐pass metabolic processes giving acceptable bioavailability. Sublingual technology is convenient for dosing in geriatric, pediatric and psychiatric patients with dysphagia. Sublingual drug delivery shows fast therapeutic action than orally ingested drugs with fewer side effects. This review highlights advantages, disadvantages, different sublingual Gland, sublingual formulation such as tablets, films drops, sprays etc, evaluation parameters.&#x0D; Keywords: Sublingual delivery, dysphagia, sublingual gland, improved bioavailability, evaluations.

Formulation and evaluation of Clopidogrel bisulfate loaded transdermal patches for anti-platelet activity

Transdermal drug delivery is an alternative route for systemic drug delivery which minimizes the absorption and increases the bioavailability. Orally clopidogrel bisulfate has a short elimination half-life (7-8 h), low oral bioavailability (50 %) undergoes extensive first pass metabolism (85 %) and frequent high doses (75 mg) are required to maintain the therapeutic level as a result. The purpose of this research was formulation and evaluation of transdermal drug delivery system of clopidogrel bisulfate using various polymers such as HPMC and EC by solvent casting technique for improvement of bioavailability of drug and reducing toxic effects. The developed transdermal patches may increase the therapeutic efficacy and reduce toxic effect of clopidogrel bisulfate. The prepared transdermal drug delivery system of clopidogrel bisulfate using different polymers such as HPMC and EC had shown good &amp; promising results for all the evaluated parameters. Based on the in vitro drug release, drug content, weight variation, tensile strength, thickness and folding endurance results formulation F2 was concluded as an optimized formulation which shows its higher percentage of drug release.&#x0D; Keyword: Clopidogrel bisulfate; Transdermal patch; TDDS; Solvent evaporation; In vitro drug release

FORMULATION AND EVALUATION OF MICROSPHERES FOR NASAL DELIVERY OF ANTI-HYPERTENSIVE DRUG

Lisinopril is used in the treatment of hypertension and heart failure in myocardial infarction and also in diabetic nephropathy. It is very poorly absorbed from GIT. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The microspheres prepared by emulsion solvent evaporation method were characterized for encapsulation efficiency, drug loading, particle size, surface morphology, degree of swelling, ex vivo mucoadhesion, drug release and ex vivo diffusion studies. Entrapment efficiency of microspheres was in range of 84.95±0.50% to 97.44±0.61% mucoadhesion was 83.76% and 94.41% and drug release up to 40 minutes was 53.66% to 88.32%. In ex vivo studies, the microspheres showed good bioavailability by nasal route compared to oral drug administration. Both in vitro and in vivo studies conclude that combination of Carbopol and HPMC based microspheres are better than single carbopol-based formulation for the delivery of lisinopril.

Challenges in nasal drug absorption: how far have we come?

The nasal route is commonly used for local delivery of drugs to treat inflammatory conditions. It is also an attractive route for systemic delivery of some drugs. Irrespective of intended use, administered drugs must permeate the epithelial or olfactory membrane to be effective. The enthusiasm for potential use of the nasal route for systemic drug delivery has not been met by comparable success. In this paper, the anatomical and physiological attributes of the nasal cavity and paranasal sinuses important for drug delivery and challenges limiting drug absorption are discussed. Efforts made so far in improving nasal drug absorption such as overcoming restrictive nasal geometry and paranasal sinuses accessibility, mucociliary clearance, absorption barriers, metabolism and drug physicochemical challenges are discussed. Highlights on future prospects of nasal drug delivery/absorption were discussed.

SITE SPECIFIC DRUG DELIVERY THROUGH NASAL ROUTE USING BIOADHESIVE POLYMERS

This review explains some aspects of mucoadhesion related to the nasal drug delivery system. On the first count, the theories of the adhesion of mucoadhesive polymers to the mucosa epithelium are described. Secondly, the characteristics and application of several widely used mucoadhesive polymers in nasal drug delivery are presented. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The aspiration of any drug delivery system is to endow with a therapeutic amount of drug to the proper site in the body to achieve promptly &amp; then uphold the desired drug concentration. That is why the drug delivery system should deliver drug at a state dictated by the needs of the body over a specified period of treatment. This idealized objective points to the two aspects most important to drug delivery, namely, spatial placement relates to targeting a drug to a specific organ or tissue while temporal delivery refers to the control of rate of drug delivery to the target tissue. Over the last few decades, the relevance of mucoadhesive polymers in nasal drug delivery systems has gained significance among pharmaceutical scientists as a means of promoting dosage form residence time in the nasal cavity as well as for improving intimacy of contact with absorptive membranes of the biological system. In addition, the improved paracellular absorption subsequent the swelling of the mucoadhesive polymers on the nasal membranes provides an important way for the absorption of the macromolecules through the nasal cavity. Keywords: Nasal route, Mucoadhesive polymers, Paracellular absorption,

The Development, Evaluation and In Vitro Release Study of the Terbinafine Transdermal Patch

Transdermal drug delivery is an alternative route for systemic drug delivery, which minimizes the absorption and increase the bioavailability. Orally Terbinafine undergoes extensive metabolism and frequent high doses are required to maintain the therapeutic level as a result, dose development toxic effect. The purpose of this research work was to formulation and evaluation of transdermal drug delivery system of Terbinafine using various polymers such as HPMC E25, Eudragit-RS100 and PVP K25 with different proportions by solvent evaporation technique. The Fourier transform infrared study revealed no physical or chemical interactions between Terbinafine and excipients. The prepared formulations were evaluated for different physicochemical characteristics such as thickness, folding endurance, drug content, percentage moisture absorption, and percentage moisture loss. The diffusion studies were performed by using modified Franz diffusion cells. The result of dissolution studies shows that formulation, SA12 showed maximum release of 92.56% in 06 h, whereas SA22 showed minimum release of 45.89% in 06 h. Based on the drug release and physicochemical values obtained the formulation SA 12 is considered as an optimized formulation, which shows higher percentage of drug release.

A Review-Vaginal Drug Delivery System

The vagina is an important application site for drug delivery, especially for local therapy of different diseases, such as bacterial, fungal and protozoa infections, for HIV prevention, delivery of contraceptives, spermicides or labor-inducers and for the treatment of precancerous lesions. It may also serve an alternative route for systemic drug delivery. In recent years, the vaginal route has been rediscovered as a potential route for systemic delivery of peptides and other therapeutically important macromolecules. A great deal of interest has been notice in the design and application of different dosage forms via the vaginal route. Several studies have proven that the vagina is an effective route for drug administration intended mainly for local action, but systemic effects of some drugs also can be attained. The major advantages of this route include accessibility, good blood supply, the ability to bypass first-pass liver metabolism, and permeability to large molecular weight drugs, such as peptides and proteins. This review, therefore, summarizes various vaginal drug delivery systems with an introduction to vaginal physiology and factors affecting drug absorption from the vaginal route.

Development and Evaluation of Intranasal Mucoadhesiv Microspheres of Neostigmine Bromide

Purpose: Neostigmine bromide, a cholinesterase inhibitor is conventionally given by oral route for the treatment of myasthenia gravis. However, it is very poorly absorbed from gastro-intestinal tract. Intranasal administration is an ideal alternative to the parenteral route for systemic drug delivery. Formulating multiparticulate system with mucoadhesive polymers may provide a significant increase in the nasal residence time. The aim of the present approach was to overcome the drawbacks of the conventional dosage forms of Neostigmine Bromide by formulating intranasal microspheres with Carbopol 974P NF and HPMC K15 M along with film forming polymer ethyl cellulose. Methods: The microspheres were prepared by emulsion solvent evaporation method. The prepared microspheres were characterized for encapsulation efficiency, drug loading, particle size, and surface morphology, degree of swelling, in-vitro mucoadhesion, drug release, in-vivo studies and stability studies. Results: Formulations IN 1 and IN 5 displayed the best results for Carbopol and HPMC based microspheres respectively. Entrapment efficiency was 75.74±0.50% and 70.27±0.61%; mucoadhesion was 98.5% and 85.3%; and drug release up to 8 h was 87.86% and 84.5% for IN 1 and IN 5 respectively. In-vivo studies revealed that the formulations IN 1 and IN 5 showed good bioavailability compared to oral drug administration. Conclusion: Both in-vitro and in-vivo studies conclude that Carbopol based microspheres are better than HPMC based microspheres for the delivery of Neostigmine Bromide.

A review on mucoadhesive polymer used in nasal drug delivery system

This update review is on mucoadhesive polymers used in nasal dosage forms. The nasal mucosa provides a potentially good route for systemic drug delivery. One of the most important features of the nasal route is that it avoids first-pass hepatic metabolism, thereby reducing metabolism. The application of mucoadhesive polymers in nasal drug delivery systems has gained to promote dosage form residence time in the nasal cavity as well as improving intimacy of contact with absorptive membranes of the biological system. The various new technology uses in development of nasal drug delivery dosage forms are discussed. The various dosage forms are vesicular carriers (liposome, noisome), nanostructured particles, prodrugs, in situ gelling system with special attention to in vivo studies.

Investigation of the dynamic process during spray-drying to improve aerodynamic performance of inhalation particles

Particle-tailoring technique requires significant improvement for wide use of pulmonary route for systemic drug delivery. In this study, the spray-dry method was used to prepare particles using maltose as a model component, with focus on interpretation of the dynamic process during the spray-drying. High-speed camera observation proved that the time required for particle formation was assumed to be on the millisecond scale. The surface tension at 10 ms was found to correlate well with both the size of the droplet produced from the spray nozzle and that of the solid particles. The surfactant molecules accumulated spontaneously on the particle surface to improve surface characteristics, including dispersity and hygroscopicity. Addition of polymer molecules made the particle surface rough, which significantly improved particle dispersity. Good correlation was found between the surface roughness and the aerodynamic performance of the particles, which was determined by a cascade impactor. The particle morphology was interpreted in terms of the mass transport of each component during the drying process. This excipient approach seems to be a promising method to prepare fine drug particles of high dispersity for achieving an efficient pulmonary drug delivery.

Safety and efficacy of intranasal ketamine for acute postoperative pain

Summary Background Subanaesthetic doses of ketamine are analgesic. Intranasal administration offers a non-invasive route for systemic drug delivery. We evaluated the safety and analgesic efficacy of intranasal ketamine in treating moderate-to-severe, acute postoperative pain in the molar extraction model. Methods Intranasal ketamine (10 mg, 30 mg, and 50 mg) and placebo were evaluated in a randomised, double-blind, single-dose, parallel study in 40 patients undergoing removal of 2–4 impacted third molars. Analgesic efficacy was assessed over a 3 h period following drug administration. Safety was evaluated through adverse event reporting, vital signs, pulse oximetry, nasal assessments, and a standard dissociative side effects questionnaire. Results Ketamine delivered intranasally was well tolerated. Statistically significant analgesia, superior to placebo, was observed with the highest dose tested, 50 mg, over a 3 h period. Rapid onset of analgesia was reported ( Conclusion Intranasal ketamine may offer a safe, nonopioid, well-tolerated, needle-free analgesic with efficacy in moderate-to-severe acute pain.

Intravail™: highly effective intranasal delivery of peptide and protein drugs

Recent development of a new class of patented alkylsaccharide transmucosal delivery enhancement agents, collectively designated as Intravail™ (Aegis Therapeutics) absorption enhancers, has created opportunities for new therapeutic options across a broad spectrum of human diseases. Intravail absorption enhancers provide unsurpassed intranasal bioavailabilities, comparable to those that are achieved by injection for protein, peptide and other macromolecular therapeutics. These novel, highly effective and non-irritating excipients circumvent the two primary limitations of intranasal drug delivery, namely mucosal irritation and poor bioavailability, and offer the promise of more convenient, more effective and safer therapeutics for patients and physicians alike. For pharmaceutical companies, Intravail provides a means to capitalise on two important industry dynamics: rapidly growing industry interest in commercialising peptide and protein drugs, and increasing interest in, and use of, the intranasal route for systemic drug delivery.