Intranasal Drug Delivery Research Articles

Nose-to-Heart Approach: Unveiling an Alternative Route of Acute Treatment.

Intranasal (IN) administration has emerged as a novel approach for rapid systemic absorption, with potential applicability in the management of acute cardiovascular events. This review explores the evolution of IN cardiovascular pharmacotherapy, emphasizing its potential in achieving systemic effects and bypassing the first-pass metabolism associated with oral administration. The extensive vascularization of nasal mucosa and a porous endothelial basement membrane facilitate efficient drug absorption into the bloodstream. The IN route ensures a critical swift onset of action, which allows self-administration in at-home settings. For instance, etripamil nasal spray, a first-in-class formulation, exemplifies the therapeutic potential of this approach in the treatment of spontaneous supraventricular tachycardia. The review critically assesses studies on IN formulations for angina, acute myocardial infarction, hypertensive episodes, and cardiac arrhythmias. Preclinical evaluations of beta-blockers, calcium-channel blockers, and antianginal drugs demonstrate the feasibility of IN administration for acute cardiovascular events. A small number of clinical trials have revealed promising results, emphasizing the superiority of IN drug delivery over oral administration in terms of bioavailability and onset of action. Unambiguously, the limited clinical trials and patient enrollment pose challenges in generalizing experimental outcomes. However, the nose-to-heart approach has clinical potential.

Assessing Nasal Epithelial Dynamics: Impact of the Natural Nasal Cycle on Intranasal Spray Deposition.

This study investigated the intricate dynamics of intranasal spray deposition within nasal models, considering variations in head orientation and stages of the nasal cycle. Employing controlled delivery conditions, we compared the deposition patterns of saline nasal sprays in models representing congestion (N1), normal (N0), and decongestion (P1, P2) during one nasal cycle. The results highlighted the impact of the nasal cycle on spray distribution, with congestion leading to confined deposition and decongestion allowing for broader dispersion of spray droplets and increased sedimentation towards the posterior turbinate. In particular, the progressive nasal dilation from N1 to P2 decreased the spray deposition in the middle turbinate. The head angle, in conjunction with the nasal cycle, significantly influenced the nasal spray deposition distribution, affecting targeted drug delivery within the nasal cavity. Despite controlled parameters, a notable variance in deposition was observed, emphasizing the complex interplay of gravity, flow shear, nasal cycle, and nasal morphology. The magnitude of variance increased as the head tilt angle increased backward from upright to 22.5° to 45° due to increasing gravity and liquid film destabilization, especially under decongestion conditions (P1, P2). This study's findings underscore the importance of considering both natural physiological variations and head orientation in optimizing intranasal drug delivery.

Quality by design approach for development and characterization of gabapentin-loaded solid lipid nanoparticles for intranasal delivery: In vitro, ex vivo, and histopathological evaluation.

"Quality by Design" (QbD) is a novel approach to product development that involves understanding the product and process, as well as the relationship between critical quality attributes (CQA) and critical process parameters (CPP). This study aimed to optimize the gabapentin-loaded solid lipid nanoparticle formulation (GP-SLN) using a QbD approach and evaluate in vitro and ex vivo performance. The GP-SLN formulation was created using the microemulsion method by combining Gelucire 48/16, Tween 80, and Plurol Oleique CC 497. The Box-Behnken experimental design was adopted to investigate the effects of independent factors on dependent factors. The GP-SLN formulation was assessed based on particle size and distribution, zeta potential, morphology, entrapment efficiency, release kinetics, permeation parameters, stability, and nasal toxicity. The nanoparticles had a cubical shape with a particle size of 185.3±45.6 nm, a zeta potential of -24±3.53 mV, and an entrapment efficiency of 82.57±4.02%. The particle size and zeta potential of the GP-SLNs remained consistent for 3 months and followed Weibull kinetics with a significantly higher ex vivo permeability (1.7 fold) than a gabapentin solution (GP-SOL). Histopathology studies showed that intranasal administration of the GP-SLN formulation had no harmful effects. The current study reports the successful development of a GP-SLN formulation using QbD. A sustained release of GP was achieved and its nasal permeability was increased. Solid lipid nanoparticles with optimum particle size and high entrapment efficiency may offer a promising approach for the intranasal delivery of drugs.

Formulation and Characterization of Intranasal Drug Delivery of Frovatriptan-Loaded Binary Ethosomes Gel for Brain Targeting.

Frovatriptan succinate (FVT) is an effective medication used to treat migraines; however, available oral formulations suffer from low permeability; accordingly, several formulations of FVT were prepared. Prepare, optimize, and evaluate FVT-BE formulation to develop enhanced intranasal binary nano-ethosome gel.‎. Binary ethosomes were prepared using different concentrations of phospholipid PLH90, ethanol, propylene glycol, and cholesterol by thin film hydration and characterized by particle size, zeta potential, and entrapment efficiency. Furthermore, in-vitro, in-vivo, ex-vivo, pharmacokinetics, and histopathological studies were done. Regarding FVT-loaded BE, formula (F9) demonstrated the best parameters from the other formulas; with the lowest particle size (154.1±4.38‎ nm), lowest PDI (‎0.213±0.05), highest zeta potential (‎-46.94±1.05), and highest entrapment efficiency (89.34±2.37%). Regarding gel formulation, G2 showed the best gel formula with drug content (‎99.82±0.02‎%) and spreadability (12.88 g/cm2). In-vitro study results showed that, in the first 30 minutes, around 22.3% of the medication is released, whereas, after 24 hours, about 98.56% is released in G2. Based on enhancing the bioavailability and sustaining the drug release, it can be concluded that the Frovatriptan-Loaded Binary ethosome Gel as nano-delivery was developed as a promising non-invasive drug delivery system for treating migraine.

Intranasal Drug Delivery by Nanotechnology: Advances in and Challenges for Alzheimer's Disease Management.

Alzheimer's disease, a progressive neurodegenerative condition, is characterized by a gradual decline in cognitive functions. Current treatment approaches primarily involve the administration of medications through oral, parenteral, and transdermal routes, aiming to improve cognitive function and alleviate symptoms. However, these treatments face limitations, such as low bioavailability and inadequate permeation. Alternative invasive methods, while explored, often entail discomfort and require specialized assistance. Therefore, the development of a non-invasive and efficient delivery system is crucial. Intranasal delivery has emerged as a potential solution, although it is constrained by the unique conditions of the nasal cavity. An innovative approach involves the use of nano-carriers based on nanotechnology for intranasal delivery. This strategy has the potential to overcome current limitations by providing enhanced bioavailability, improved permeation, effective traversal of the blood-brain barrier, extended retention within the body, and precise targeting of the brain. The comprehensive review focuses on the advancements in designing various types of nano-carriers, including polymeric nanoparticles, metal nanoparticles, lipid nanoparticles, liposomes, nanoemulsions, Quantum dots, and dendrimers. These nano-carriers are specifically tailored for the intranasal delivery of therapeutic agents aimed at combatting Alzheimer's disease. In summary, the development and utilization of intranasal delivery systems based on nanotechnology show significant potential in surmounting the constraints of current Alzheimer's disease treatment strategies. Nevertheless, it is essential to acknowledge regulatory as well as toxicity concerns associated with this route; meticulous consideration is required when engineering a carrier. This comprehensive review underscores the potential to revolutionize Alzheimer's disease management and highlights the importance of addressing regulatory considerations for safe and effective implementations. Embracing this strategy could lead to substantial advancements in the field of Alzheimer's disease treatment.

In silico exploration of venlafaxine, a potential non-tricyclic antidepressant in a liposomal formulation for nose-to-brain drug delivery

Objective Non-tricyclic antidepressants (non-TCAs) work by preventing the intake of norepinephrine and serotonin. Therefore, the aim of this study was to identify a potent non-TCAs and to develop liposomal formulation, characterize and to determine the drug release study across model of dialysis membrane via in vitro and in silico techniques. Methods The in silico docking analysis identified venlafaxine (VLF) as the best non-TCAs with the depressant targets (PDB ID: 3PBL and 4BVN). VLF-loaded liposomal formulation was prepared by the thin-film hydration technique and characterized by physicochemical properties, including entrapment efficacy, in vitro drug release, particle size analysis, and FTIR. Moreover, this article also compares VLF and VLF-loaded with liposome carriers (LPs) based on nose-to-brain drug delivery approaches to treating depression. Results Drug release profiles of the optimal liposomal formulation of VLF-LPs were examined in the high entrapment efficiency 94.13 ± 1.20% was attained at 224 nm, composed of spherical particles having a mean particle size of 191 ± 2.0 nm, a polydispersity index of 0.281 ± 0.06 and zeta potential of −20.3 mV. The best formulation of VLF-LPs was more effective than oral VLF treatment, as shown by the in vitro drug release data. Conclusion The results show that the VLF-LPs formulation is a promising potential platform for application in nose-to-brain drug delivery. Thus, highlighting the robustness of the intranasal drug delivery system with enhanced pharmaceutical properties, efficacy, and bioavailability for the anti-depression effect.

Improved Olfactory Deposition of Theophylline Using a Nanotech Soft Mist Nozzle Chip.

Currently, nasal administration of active pharmaceutical ingredients is most commonly performed using swirl-nozzle-based pump devices or pressurized syringes. However, they lead to limited deposition in the more active regions of the nasal cavity, especially the olfactory region, which is crucial for nose-to-brain drug delivery. This research proposes to improve deposition in the olfactory region by replacing the swirl nozzle with a nanoengineered nozzle chip containing micrometer-sized holes, which generates smaller droplets of 10-50 μm travelling at a lower plume velocity. Two nanotech nozzle chips with different hole sizes were tested at different inhalation flow rates to examine the deposition patterns of theophylline, a hyposmia treatment formulation, using a nasal cavity model. A user study was also conducted and showed that the patient instructions influenced the inhalation flow rate characteristics. Targeted flow rates of between 0 and 25 L/min were used for the in vitro deposition study, yielding 21.5-31.5% olfactory coverage. In contrast, the traditional swirl nozzle provided only 10.8% coverage at a similar flow rate. This work highlights the potential of the nanotech soft mist nozzle for improved intranasal drug delivery, particularly to the olfactory region.

Evaluation of nasal delivery systems of olanzapine by desorption electrospray ionization mass spectrometry imaging

Nose-to-brain delivery presents an attractive administration route for neuroactive drugs that suffer from compromised bioavailability or fail to pass the blood–brain barrier. However, the conventional gauge of effectiveness for intranasal delivery platforms primarily involves detecting the presence of the administered drug within the brain, with little insight into its precise localization within brain structures. This may undermine the therapeutic efficacy of drugs and hinder the design of systems that target specific brain regions. In this study, we designed two intranasal delivery systems for the antipsychotic drug, olanzapine, and evaluated its distribution in the rat brain following intranasal administration. The first evaluated system was an olanzapine-loaded microemulsion and the second one was nanoparticulate aqueous dispersion of olanzapine. Both systems exhibited characteristics that render them compatible for intranasal administration, and successfully delivered olanzapine to the brain. We further employed an ambient mass spectrometry imaging method, called desorption electrospray ionization mass spectrometry imaging, to visualize the signal intensity of olanzapine in different brain regions following the intranasal administration of these two systems. Substantial variations in the distribution patterns of olanzapine across various brain structures were revealed, potentially highlighting the importance of mass spectrometry imaging in designing and evaluating intranasal drug delivery platforms.

Preparation and Optimization of Bovine Serum Albumin Nanoparticles as a Promising Gelling System for Enhanced Nasal Drug Administration.

Bovine serum albumin (BSA) has been used extensively as a suitable carrier system for alternative drug delivery routes, such as nasal administration. However, the optimization of BSA nanoparticles with respect to their nasal applicability has not been widely studied. The present study focuses on the characterization of BSA nanoparticles prepared using the desolvation method, followed by a gelation process to facilitate intranasal drug delivery. The results demonstrated that the ratio of BSA and the desolvating agent, ethanol, played a critical role in the nanoparticle characteristics of the BSA nanogel matrices (BSA-NGs). Based on the gelling properties, the formulations of BSA-NG 2, BSA-NG 4, and BSA-NG 6 were selected for further investigation. The Raman spectra confirmed that there were no specific changes to the secondary structures of the BSA. The mucoadhesion studies revealed moderately high mucoadhesive properties, with a mucin binding efficiency (MBE) value of around 67%, allowing the dose to avoid elimination due to rapid mucociliary clearance of the nasal passage. Via studying the nexus of the carrier system, BSA-NGs loaded with dexamethasone as a model drug were prepared and evaluated by differential scanning calorimetry (DSC) and thermal gravimetry (TG), ascertaining that no ethanol remained in the samples after the freeze-drying process. Furthermore, the viscosity measurements exhibited moderate viscosity, which is suitable for nasal liquid preparations. The in vitro release studies performed with a simulated nasal electrolyte solution (SNES) medium showed 88.15-95.47% drug release within 4 h. In conclusion, BSA nanoparticle gelling matrices can offer potential, value-added drug delivery carriers for improved nasal drug administration.

Intranasal delivery of sunitinib: A new therapeutic approach for targeting angiogenesis of glioblastoma

Glioblastoma multiforme (GBM) is one of the most vascular among solid tumors, and despite the use of multimodal therapies, the survival of these patients is poor. In order to target angiogenesis in GBM as a promising strategy, an antiangiogenic drug is required. This study was designed to evaluate the effects of sunitinib, a multityrosine kinase inhibitor with tumor proliferation and angiogenesis inhibitory properties, on GBM-bearing rats. Given the ineffective drug delivery to the brain due to the presence of the blood-brain barrier (BBB), intra-nasal (IN) drug delivery has recently been considered as a non-invasive method to bypass BBB. Therefore, in the current study, IN was used as an ideal method for the delivery of sunitinib to the brain, and the effects of this method were also compared to the OR administration of the sunitinib. GBM was induced in the brain of male Wistar rats, and they were randomly divided into 4 groups; IN-STB (sunitinib intranasal delivery), IN-sham (placebo intranasal delivery), OR-STB (sunitinib oral delivery) and OR-sham (placebo oral delivery). After the end of the treatment period, an MRI of animals' brains showed a reduction in tumor growth in the treatment groups. Immunohistochemistry revealed that sunitinib inhibits angiogenesis in GBM in both OR and IN delivery methods. Analysis of liver tissue and enzymes showed that IN delivery of sunitinib had less hepatotoxicity than the OR method. Overall, it was found that IN sunitinib delivery could be used as a potential non-hepatotoxic alternative for the treatment of GBM.

Intranasal drug delivery in pediatric emergency departments: brief review and future outlook

This review aims to provide an overview and update of current literature on the use of intranasal (IN) drug delivery in pediatric emergency medicine (PEM), in terms of the anatomy, physiology, pharmacokinetics, limitations, drug delivery methods, necessary training, safety, contraindications, effectiveness, current indications and trends, and implications for clinical practice and future developments in IN drug administration. We evaluate how IN medication use in PEM has recently evolved, what recent research has revealed about the utility of IN drug delivery in PEM, and what the future of IN drug delivery might look like.

Porous silicon embedded in a thermoresponsive hydrogel for intranasal delivery of lipophilic drugs to treat rhinosinusitis

Intranasal delivery is the most preferred route of drug administration for treatment of a range of nasal conditions including chronic rhinosinusitis (CRS), caused by an infection and inflammation of the nasal mucosa. However, localised delivery of lipophilic drugs for persistent nasal inflammation is a challenge especially with traditional topical nasal sprays. In this study, a composite thermoresponsive hydrogel is developed and tuned to obtain desired rheological and physiochemical properties suitable for intranasal administration of lipophilic drugs. The composite is comprised of drug-loaded porous silicon (pSi) particles embedded in a poloxamer 407 (P407) hydrogel matrix. Mometasone Furoate (MF), a lipophilic corticosteroid (log P of 4.11), is used as the drug, which is loaded onto pSi particles at a loading capacity of 28 wt%. The MF-loaded pSi particles (MF@pSi) are incorporated into the P407-based thermoresponsive hydrogel (HG) matrix to form the composite hydrogel (MF@pSi-HG) with a final drug content ranging between 0.1 wt% to 0.5 wt%. Rheomechanical studies indicate that the MF@pSi component exerts a minimal impact on gelation temperature or strength of the hydrogel host. The in-vitro release of the MF payload from MF@pSi-HG shows a pronounced increase in the amount of drug released over 8 h (4.5 to 21-fold) in comparison to controls consisting of pure MF incorporated in hydrogel (MF@HG), indicating an improvement in kinetic solubility of MF upon loading into pSi. Ex-vivo toxicity studies conducted on human nasal mucosal tissue show no adverse effect from exposure to either pure HG or the MF@pSi-HG formulation, even at the highest drug content of 0.5 wt%. Experiments on human nasal mucosal tissue show the MF@pSi-HG formulation deposits a quantity of MF into the tissues within 8 h that is >19 times greater than the MF@HG control (194 ± 7 μg of MF/g of tissue vs. <10 μg of MF/g of tissue, respectively).

A Potential Strategy for Treating Parkinson's Disease Through Intranasal Nanoemulsions.

Intranasal delivery has great potential to cross the blood-brain barrier and deliver the drug molecule into the central nervous system faster than the traditional methods. The olfactory neuronal and trigeminal pathways both are involved in intranasal delivery. The nano-technology is an innovative strategy for the nose to brain delivery. The mucoadhesive nanoemulsion formulation is a modified technology that increases the duration of drug accumulation and provides prolonged delivery at a targeted site. The nanoemulsion formulation oil, surfactant, and co-surfactant components maintain lower surface tension and particle coalescence. The globule dimension and zeta potential are affected in brain targeting. The globule size of the innovative formulation should be < 200 nm for drug permeation because, in humans, the average axon magnitude ranges from around 100 to 700 nm. Furthermore, modified technology of nanoemulsions like nanogel and nanoemulsion in-situ gel provide a great advantage to cure neurodegenerative disorders. Therefore, focusing on the innovative pharmaceutical approaches of nanoemulsion in intranasal drug delivery, the current review provides insight into the applications of nanoemulsion in neurodegenerative disorders like Parkinson's disease, which are due to the depletion of dopamine in substania nigra resulting in cardinal motor activity bradykinesia and tremors. The review also touches upon the pathways for intranasal delivery of nanoemulsion, the pathogenesis of Parkinson's disease, and the future direction of the research on intranasal nanoemulsion.

Design and Evaluations of a Nanostructured Lipid Carrier Loaded with Dopamine Hydrochloride for Intranasal Bypass Drug Delivery in Parkinson's disease

Aim- The goal of this study is to optimization and evaluation of dopamine-loaded NLC (NLC-DOPA) for achieve dopamine concentrations into brain for treatment of Parkinson's disease which causes progressive neuronal death. Method- NLC-DOPA prepared by homogenization method using solid lipids (Cholesterol and Soya lecithin), liquid lipid (Oleic acid) and surfactant (Poloxamer- 188) as major excipients, optimized by central composite design using design expert-13 software. The optimized formulations were characterized by particle size, zeta potential, entrapment efficiency, SEM, TEM, FTIR, DSC, XRD, stability study and in-vitro drug release. The histopathology of rat brain tissues and goat nasal tissues were performed. The ex-vivo (permeability and nasal ciliotoxicity study) and in vivo pharmacodynamics study were also accomplished to determine its efficacy and potency of NLC. Result- The NLC-DOPA formulations were optimized in particle size and (EE)% with range from 85.53 ± 0.703 to 106.11 ± 0.822 nm and 82.17 ± 0.794 to 95.45 ± 0.891%, respectively. The optimized formulation F11 showing best goodness-fitted model kinetic, followed by Korsmeyer-Peppas equation and zero order kinetic. The SEM and TEM confirmed the spherical and smooth morphology of formulation. FTIR and DSC spectra were given compatibility of compound and XRD diffractograms confirmed the amorphous nature. An ex-vivo study was showed the high permeability coefficient (6.67*10−4 cm/min, which is twice, compare to pure drug) and there was no damage in nasal mucosa, confirmed by the ciliotoxicity study. In-vivo study was shown significant effects of optimized NLC-DOPA on locomotor activity, force-swimming test and neurochemical assessment using rotenone induced Parkinson’s model on Albino wistar rats. Conclusion- NLC-DOPA was prepared and optimized successfully with increased bioavailability of drug from the NLC into brain with reduce toxicity in effective treatment of Parkinson’s disease.

Biomedical applications of artificial exosomes for intranasal drug delivery.

Intranasal administration offers a feasible, non-invasive method of delivering therapeutic drugs to the brain, allowing therapeutic pharmaceuticals to be administered directly to the central nervous system by bypassing the blood-brain barrier. Furthermore, exosomes are naturally occurring cell-derived nanovesicles that can serve as carriers for a variety of chemical compounds. Many studies have focused on artificial exosomes as innovative medication delivery methods. As a result, trans-nasal delivery of artificial exosomes might be employed to treat brain illnesses in a novel method. This review will outline the drug delivery mechanism of artificial extracellular vesicles, emphasize its advantages as a nasal drug carrier, particularly its application as a novel nanocarriers in brain diseases, and focus on its prospective application in chronic inflammatory nose disorders. Finally, artificial exosomes may become a unique drug delivery mode for clinical therapeutic usage.

Design and development of donepezil hydrochloride loaded nanostructured lipid carriers for efficient management of Alzheimer’s disease

Objective The primary objective of this study was to develop nanostructured lipid carriers of donepezil hydrochloride (DNZ HCl) for effective management of Alzheimer’s disease (AD). Significance Intranasal administration of DNZ NLC containing Nigella sativa (NS) oil as a liquid lipid may significantly improve nasal penetration and deliver the drug directly to the brain avoiding blood brain barrier (BBB). Method High pressure homogenization was used to prepare nanostructured lipid carriers (NLCs), followed by ultrasonication. Glyceryl monostearate (GMS), Tween 80, and Poloxamer 407 were used as solid lipid, surfactant and co-surfactant respectively, whereas, Nigella sativa oil was used as a liquid lipid. Result The particle size, polydispersity index and zeta potential were found to be 107.4 ± 2.64 nm, 0.25 ± 0.04 and −41.7 mV. The entrapment efficiency and drug content were found to be 70.20% and 89.05% respectively. After intranasal administration of Donepezil hydrochloride (DNZ HCl) loaded NLC’s, the maximum concentrations (Cmax) of 4.597 µg/mL in brain and 2.2583 µg/mL in blood was achieved after 1 h (Tmax). Conclusion The formulated DNZ HCl loaded NLCs significantly improved nasal penetration and enhanced drug distribution in brain resulting in a potentially effective intranasal drug delivery system for the effective management of Alzheimer’s disease.

Intranasal nanoparticulate delivery systems for neurodegenerative disorders: a review.

Neurodegenerative diseases are a significant cause of mortality worldwide, and the blood-brain barrier (BBB) poses a significant challenge for drug delivery. An intranasal route is a prominent approach among the various methods to bypass the BBB. There aredifferent pathways involved in intranasal drug delivery. The drawbacks of this method include mucociliary clearance, enzymatic degradationand poor drug permeation. Novel nanoformulations and intranasal drug-delivery devices offer promising solutions to overcome these challenges. Nanoformulations include polymeric nanoparticles, lipid-based nanoparticles, microspheres, liposomes and noisomes. Additionally, intranasal devices could be utilized to enhance drug-delivery efficacy. Therefore, intranasal drug-delivery systems showpotential for treating neurodegenerative diseases through trigeminal or olfactory pathways, which can significantly improve patient outcomes.

Synthesis of an insulin-loaded mucoadhesive nanoparticle designed for intranasal administration: focus on new diffusion media.

Intranasal administration is a drug delivery approach to provide a non-invasive pharmacological response in the central nervous system with relatively small peripheral side effects. To improve the residence time of intranasal drug delivery systems in the nasal mucosa, mucoadhesive polymers (e.g., chitosan) can be used. Here, insulin-loaded chitosan nanoparticles were synthesized and their physiochemical properties were evaluated based on requirements of intranasal administration. The nanoparticles were spherical (a hydrodynamic diameter of 165.3nm, polydispersity index of 0.24, and zeta potential of +21.6mV) that granted mucoadhesion without any noticeable toxicity to the nasal tissue. We applied a new approach using the Krebs-Henseleit buffer solution along with simulated nasal fluid in a Franz's diffusion cell to study this intranasal drug delivery system. We used the Krebs-Henseleit buffer because of its ability to supply glucose to the cells which serves as a novel ex vivo diffusion medium to maintain the viability of the tissue during the experiment. Based on diffusion rate and histopathological endpoints, the Krebs-Henseleit buffer solution can be a substituent solution to the commonly used simulated nasal fluid for such drug delivery systems.

ROLE OF NASYA TO REGULATE H-P-O AXIS IN THE MANAGEMENT OF ARTAVA KSHAYA

Nasya karma, also known as intranasal drug delivery, is the specific treatment methodology briefly explained in Ayurveda under Panchakarma. Nasya karma has been recognised as an important form of treatment for cleansing of Urdhava Jatrugata doshas (supra clavicular part of body), palliation of diseases of head and neck and it alleviates Vata kapha dosha. Normal menstruation requires integration of H-P-O axis with a functional uterus, any break in this axis creates menstrual problems in which the most common one in today’s era is Artava kshaya. The term Artava has many meanings like menstrual blood, ovum and ovarian hormones. Artava kshaya can be correlated with oligomenorrhoea or hypomenorrhoea by their sign and symptoms. As per Ayurveda Nasa is considered as the gateway of Sirah i.e., brain hence Nasya would be the appropriate Shodhana procedure to regulate H-P-O axis and establishment of normal menstrual cycle.

Optimizing Absorption for Intranasal Delivery of Drugs Targeting the Central Nervous System Using Alkylsaccharide Permeation Enhancers.

Intranasal delivery of drugs offers several potential benefits related to ease of delivery, rapid onset, and patient experience, which may be of particular relevance to patients with central nervous system (CNS) conditions who experience acute events. Intranasal formulations must be adapted to address anatomical and physiological characteristics of the nasal cavity, including restricted dose volume, limited surface area, and barriers to mucosal absorption, in addition to constraints on the absorption window due to mucociliary clearance. Development of an effective formulation may utilize strategies including the addition of excipients to address the physicochemical properties of the drug within the constraints of nasal delivery. Dodecyl maltoside (DDM) and tetradecyl maltoside are alkylsaccharide permeation enhancers with well-established safety profiles, and studies have demonstrated transiently improved absorption and favorable bioavailability of several compounds in preclinical and clinical trials. Dodecyl maltoside is a component of three US Food and Drug Administration (FDA)-approved intranasal medications: diazepam for the treatment of seizure cluster in epilepsy, nalmefene for the treatment of acute opioid overdose, and sumatriptan for the treatment of migraine. Another drug product with DDM as an excipient is currently under FDA review, and numerous investigational drugs are in early-stage development. Here, we review factors related to the delivery of intranasal drugs and the role of alkylsaccharide permeation enhancers in the context of approved and future intranasal formulations of drugs for CNS conditions.