Nasal Drug Research Articles

Regional deposition of mometasone furoate nasal spray suspension in humans.

Nasal deposition studies can demonstrate whether nasal sprays treating allergic rhinitis and polyposis reach the ciliated posterior nasal cavity, where turbinate inflammation and other pathology occurs. However, quantifying nasal deposition is challenging, because in vitro tests do not correlate to human nasal deposition; gamma scintigraphy studies are thus used. For valid data, the radiolabel must distribute, as the drug, into different-sized droplets, remain associated with the drug in the formulation after administration, and not alter its deposition. Some nasal deposition studies have demonstrated this using homogenous solutions. However, most commercial nasal sprays are heterogeneous suspensions. Using mometasone furoate nasal suspension (MFS), we developed a technique to validate radiolabel deposition as a surrogate for nasal cavity drug deposition and characterized regional deposition and nasal clearance in humans. Mometasone furoate (MF) formulation was spiked with diethylene triamine pentacaetic acid. Both unlabeled and radiolabeled formulations (n = 3) were sprayed into a regionally divided nasal cast. Drug deposition was quantified by high pressure liquid chromatography within each region; radiolabel deposition was determined by gamma camera. Healthy subjects (n = 12) were dosed and imaged for six hours. Scintigraphic images were coregistered with magnetic resonance imaging scans to quantify anterior and posterior nasal cavity deposition and mucociliary clearance. The ratio of radiolabel to unlabeled drug was 1.05 in the nasal cast and regionally appeared to match, indicating that in vivo radiolabel deposition could represent drug deposition. In humans, MFS delivered 86% (9.2) of metered dose to the nasal cavity, approximately 60% (9.1) of metered dose to the posterior nasal cavity. After 15 minutes, mucociliary clearance removed 59% of the initial radiolabel in the nasal cavity, consistent with clearance rates from the ciliated posterior surface. MFS deposited significant drug into the posterior nasal cavity. Both nasal cast validation and mucociliary clearance confirm the radiolabel deposition distribution method accurately represented corticosteroid nasal deposition.

Gellan gum-based mucoadhesive microspheres of almotriptan for nasal administration: Formulation optimization using factorial design, characterization, and in vitro evaluation.

Background:Almotriptan malate (ALM), indicated for the treatment of migraine in adults is not a drug candidate feasible to be administered through the oral route during the attack due to its associated symptoms such as nausea and vomiting. This obviates an alternative dosage form and nasal drug delivery is a good substitute to oral and parenteral administration.Materials and Methods:Gellan gum (GG) microspheres of ALM, for intranasal administration were prepared by water-in-oil emulsification cross-linking technique employing a 23 factorial design. Drug to polymer ratio, calcium chloride concentration and cross-linking time were selected as independent variables, while particle size and in vitro mucoadhesion of the microspheres were investigated as dependent variables. Regression analysis was performed to identify the best formulation conditions. The microspheres were evaluated for characteristics such as practical percentage yield, particle size, percentage incorporation efficiency, swellability, zeta potential, in vitro mucoadhesion, thermal analysis, X-ray diffraction study, and in vitro drug diffusion studies.Results:The shape and surface characteristics of the microspheres were determined by scanning electron microscopy, which revealed spherical nature and nearly smooth surface with drug incorporation efficiency in the range of 71.65 ± 1.09% – 91.65 ± 1.13%. In vitro mucoadhesion was observed the range of 79.45 ± 1.69% – 95.48 ± 1.27%. Differential scanning calorimetry and X-ray diffraction results indicated a molecular level dispersion of drug in the microspheres. In vitro drug diffusion was Higuchi matrix controlled and the release mechanism was found to be non-Fickian. Stability studies indicated that there were no significant deviations in the drug content, in vitro mucoadhesion and in vitro drug diffusion characteristics.Conclusion:The investigation revealed promising potential of GG microspheres for delivering ALM intranasally for the treatment of migraine.

Study of mucoadhesive microsphere of pirfenidone for nasal drug delivery

Study of mucoadhesive microsphere of pirfenidone for nasal drug delivery

Bioavailability enhancement of ondansetron after nasal administration of Caesalpinia pulcherrima-based microspheres

Context: Natural polymers have attracted a great deal of attention for use as potential carriers in site-specific delivery over past decades. Mucoadhesive microspheres are useful tools for nasal drug delivery. Objectives: To prepare and evaluate mucoadhesive microspheres as mode for nasal delivery of ondansetron using Caesalpinia pulcherrima galactomannan (CPG). Materials and methods: Conventional spray-dried CPG nasal microspheres loaded with ondansetron for intranasal drug delivery in order to avoid the first pass metabolism with improved therapeutic efficiency in treatment of nausea and vomiting as an alternative therapy to parenterals. Developed microspheres were evaluated for characteristics like particle size, entrapment efficiency, zeta potential, swelling ability, in-vitro mucoadhesion, in-vitro drug release, DSC, XRD study and histopathological evaluation of tissue. CPG-based ondansetron microspheres were studied in rabbits for screening nasal absorption potential of nasal formulation. Results: Developed nasal microspheres possess entrapment efficiency of 80–89%, higher mucoadhesion of 72–84% across goat nasal mucosa. In-vivo study showed that microspheres based on mucoadhesive polymer were able to promote quick drug absorption as well as enhanced bioavailability of drug. Discussion: Histopathological studies evaluated biocompatible and nontoxic nature of CPG in nasal cavity. Developed mucoadhesive microspheres by nasal route showed enhancement of bioavailability as compared to oral route in rabbits. Conclusion: CPG-based mucoadhesive microspheres can successfully deliver ondansetron intranasally, sustain its effect, avoid first pass effect, an alternative route of administration to injection and thus enhance systemic bioavailability of ondansetron hydrochloride.

Synthesis and in vitro characterization of entirely S-protected thiolated pectin for drug delivery

The study was aimed to synthesize a thiolated polymer (thiomer) that is resistant to oxidation in solutions above pH 5. In order to protect a pectin–cysteine conjugate against premature oxidation, the thiomer was S-protected by a disulfide connected leaving group. Therefore, 2-mercaptonicotinic acid was first coupled to l-cysteine by a disulfide exchange reaction and the purified product was subsequently attached to pectin by a carbodiimide mediated amid bond formation. The obtained fully S-protected thiolated pectin was in vitro characterized with respect to co- and mucoadhesive properties and stability toward oxidation. The results indicated a 1.8-fold and 2.3-fold enhanced disintegration time at pH 6.8 of the S-protected thiolated pectin (Pec–Cys–MNA) compared to thiolated pectin (Pec–Cys) and unmodified pectin (Pec). Moreover, rheological measurements of polymer/mucus mixtures showed a 1.6-fold (compared to Pec–Cys) and 6.7-fold (compared to Pec) increased dynamic viscosity of Pec–Cys–MNA. On the other hand, in the presence of a strong oxidizing agent such as H2O2 (0.3% v/v), no increase in viscosity of Pec–Cys–MNA could be observed. A 6-month experiment also demonstrated the long-term stability of a liquid formulation based on Pec–Cys–MNA. Further investigations proved that the first time all thiol groups on a thiolated polymer could be protected owing to the novel synthesis. Accordingly, these features may help to develop thiomer based liquid or gel formulations targeting mucosal surfaces such as nasal, ocular or vaginal drug delivery systems.

Formulation and Evaluation of Niosomal Nasal Drug Delivery System of Folic Acid for Brain Targeting

Nasal mucosa offers advantages to deliver drugs to brain via olfactory route thus provides rapid onset of drug action and hence faster therapeutic effect. Therefore, various strategies have been proposed to improve the delivery of different drugs to brain including liposomes, colloidal drug carriers, micelles, chimeric peptide technology and nanotechnology through nasal route. The low blood level of folates is the primary cause of depression in Alzheimer's disease. Folic acid is a water soluble vitamin showing difficulty in crossing the blood brain barrier and thus was formulated as niosomal nasal drug delivery systems to target the brain. In the present work, folic acid niosomes were prepared using different nonionic surfactants i.e., span 20, span 60, span 80, tween 20, tween 80 and cholesterol by using lipid layer hydration technique. These were evaluated for particle size, viscosity, osmotic shock, entrapment efficiency and in vitro drug release. The influence of different formulation variables such as surfactant type, surfactant concentration, and cholesterol concentration was optimized for required size distribution, viscosity, entrapment efficiency and in vitro release. The prepared niosomes were in the size range of 3.05-5.625 µm. Niosomes prepared with span 60 and cholesterol in the ratio of 1:1 (50 mg: 50 mg) shown higher entrapment efficiency of 69.42% and better in vitro drug release of 64.2% at the end of 12 hrs and therefore considered as optimized formulation. The stability studies were carried out by storing niosomes at 4±1°C and 25±1°C and showed good stability over the period of storage. The release of drug from niosomes followed anomalous diffusion and obeyed first order release kinetics. Ex-vivo perfusion studies were also performed by using rat model, about 48.15% of drug was found to be absorbed through nasal cavity at the end of 6 hrs.

Breath Powered Nasal Delivery: A New Route to Rapid Headache Relief

The nose offers an attractive noninvasive alternative for drug delivery. Nasal anatomy, with a large mucosal surface area and high vascularity, allows for rapid systemic absorption and other potential benefits. However, the complex nasal geometry, including the narrow anterior valve, poses a serious challenge to efficient drug delivery. This barrier, plus the inherent limitations of traditional nasal delivery mechanisms, has precluded achievement of the full potential of nasal delivery. Breath Powered bi-directional delivery, a simple but novel nasal delivery mechanism, overcomes these barriers. This innovative mechanism has now been applied to the delivery of sumatriptan. Multiple studies of drug deposition, including comparisons of traditional nasal sprays to Breath Powered delivery, demonstrate significantly improved deposition to superior and posterior intranasal target sites beyond the nasal valve. Pharmacokinetic studies in both healthy subjects and migraineurs suggest that improved deposition of sumatriptan translates into improved absorption and pharmacokinetics. Importantly, the absorption profile is shifted toward a more pronounced early peak, representing nasal absorption, with a reduced late peak, representing predominantly gastrointestinal (GI) absorption. The flattening and “spreading out” of the GI peak appears more pronounced in migraine sufferers than healthy volunteers, likely reflecting impaired GI absorption described in migraineurs. In replicated clinical trials, Breath Powered delivery of low-dose sumatriptan was well accepted and well tolerated by patients, and onset of pain relief was faster than generally reported in previous trials with noninjectable triptans. Interestingly, Breath Powered delivery also allows for the potential of headache-targeted medications to be better delivered to the trigeminal nerve and the sphenopalatine ganglion, potentially improving treatment of various types of headache. In brief, Breath Powered bi-directional intranasal delivery offers a new and more efficient mechanism for nasal drug delivery, providing an attractive option for improved treatment of headaches by enabling or enhancing the benefits of current and future headache therapies.

The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group Initiatives for Parenteral and Ophthalmic Drug Product (PODP)

The Product Quality Research Institute (PQRI) is a non-profit consortium of organizations working together to generate and share timely, relevant, and impactful information that advances drug product quality and development. The collaborative activities of PQRI participants have, in the case of orally inhaled and nasal drug products (OINDPs), resulted in comprehensive and widely-accepted recommendations for leachables assessments to help ensure patient safety with respect to this class of packaged drug products. These recommendations, which include scientifically justified safety thresholds for leachables, represent a significant milestone towards establishing standardized approaches for safety qualification of leachables in OINDP. To build on the success of the OINDP effort, PQRI's Parenteral and Ophthalmic Drug Products (PODP) Leachables and Extractables Working Group was formed to extrapolate the OINDP threshold concepts and best practice recommendations to other dosage forms with high concern for interaction with packaging/delivery systems. This article considers the general aspects of leachables and their safety assessment, introduces the PODP Work Plan and initial study Protocol, discusses the laboratory studies being conducted by the PODP Chemistry Team, outlines the strategy being developed by the PODP Toxicology Team for the safety qualification of PODP leachables, and considers the issues associated with application of the safety thresholds, particularly with respect to large-volume parenterals. Lastly, the unique leachables issues associated with biologics are described. The Product Quality Research Institute (PQRI) is a non-profit consortium involving industry organizations, academia, and regulatory agencies that together provide recommendations in support of regulatory guidance to advance drug product quality. The collaborative activities of the PQRI Orally Inhaled and Nasal Drug Products Leachables and Extractables Working Group resulted in a systematic and science-based approach to identify and qualify leachables, including the concept of safety thresholds. Concepts from this widely accepted approach, formally publicized in 2006, are being extrapolated to parenteral and ophthalmic drug products. This article provides an overview of extractables and leachables in drug products and biologics and discusses the PQRI Work Plan and Protocols developed by the PQRI Parenteral and Ophthalmic Drug Products Leachables and Extractables Working Group.

NOSE TO BRAIN DELIVERY OF ZIPRASIDONE MICROEMULSION: DESIGEN AND CHARACTERIZATION

Nasal administration offers an interesting promising alternative technique to the parenteral route for achieving systemic drug effects. Now a day many drugs have better systemic bioavailability through nasal route as compared to oral administration. Microemulsion is dispersed, macroscopically homogenous thermodynamically stable, optically transparent, single phase system, formed by spontaneous solubilisation of two immiscible liquid, in the presence of surfactants. Mic roemulsion offers number of advantages than drug formu lation for nasal drug delivery. Ziprasidone is lipophilic, benz - isothiazoyl - piperazine derivative, used in the treatment of schizophrenia, mania and mixed states associated with bipolar disorder. The mi croemulsion was prepared by precipitation method. The characterization of microemulsion formulation includes determination of viscosity, pH, drug content, refractive, conductivity measurement, zeta potential analysis and particle size analysis . In - vitro dr ug permeation studies were done b y using Keshary Diffusion cell. All ME formulations were shown fast drug permeat ion 99.50 % for ME 2 within 1 h and 99.40 % for ME 6 within 100 minutes since the ME 2 which is optimized on the basis of in - vitro study. Nasal mucoadhesive drug delivery system is designed with an aim to target the drug and to maintain the dosage form at its absorptio n site for a rapid onset of time. This will result in the enhancement of the absorption of the drug, which will in turn reduce the presystemic metabolism; increase the bioavailability of the drug, initiate rapid onset of action and thus will decrease the dosing frequency and dose r elated side effects of the drug . For this purpose in microemulsion system is preferred over conventional solution system.

Nasal Drug Delivery in Traditional Persian Medicine

Over one hundred different pharmaceutical dosage forms have been recorded in literatures of Traditional Persian Medicine among which nasal forms are considerable. This study designed to derive the most often applied nasal dosage forms together with those brief clinical administrations. In the current study remaining pharmaceutical manuscripts of Persia during 9th to 18th century AD have been studied and different dosage forms related to nasal application of herbal medicines and their therapeutic effects were derived. By searching through pharmaceutical manuscripts of medieval Persia, different nasal dosage forms involving eleven types related to three main groups are found. These types could be derived from powder, solution or liquid and gaseous forms. Gaseous form were classified into fumigation (Bakhoor), vapor bath (Enkebab), inhalation (Lakhlakheh), aroma agents (Ghalieh) and olfaction or smell (Shomoom). Nasal solutions were as drops (Ghatoor), nasal snuffing drops (Saoot) and liquid snuff formulations (Noshoogh). Powders were as nasal insufflation or snorting agents (Nofookh) and errhine or sternutator medicine (Otoos). Nasal forms were not applied only for local purposes. Rather systemic disorders and specially CNS complications were said to be a target for these dosage forms. While this novel type of drug delivery is known as a suitable substitute for oral and parenteral administration, it was well accepted and extensively mentioned in Persian medical and pharmaceutical manuscripts and other traditional systems of medicine as well. Accordingly, medieval pharmaceutical standpoints on nasal dosage forms could still be an interesting subject of study. Therefore, the current work can briefly show the pharmaceutical knowledge on nasal formulations in medieval Persia and clarify a part of history of traditional Persian pharmacy.

Development of Abelmoschus esculentus (Okra)-Based Mucoadhesive Gel for Nasal Delivery of Rizatriptan Benzoate

Purpose: To develop a safe mucoadhesive gel for nasal drug delivery using okra polysaccharide.Methods: Rizatriptan benzoate nasal gel was developed using natural polysaccharide obtained from the Abelmoschus esculentus. The gel formulation was characterized for pH, viscosity, mucoadhesion, and in vitro permeation. Permeation parameters obtained include drug flux (j), permeation coefficient (kP) and lag time (tL). The effect of sodium thioglycollate and sodium taurocholate on permeation of the gel formulations was evaluated using excised goat nasal mucosa.Results: Okra gel formulation showed good properties in terms of pH, viscosity and mucoadhesion. The drug was able to permeate through the goat nasal mucosa within 255 min. The test okra nasal gel, with and without enhancer, showed superior permeation properties to gels prepared with synthetic polymers - hydroxylpropyl methylcellulose (HPMC) and sodium carboxymethyl cellulose (NaCMC). For example, drug flux (j) of okra nasal gel formulation and gel formulations made with HPMC and NaCMC was 134.8, 120.9 and 84.8, respectively.Conclusion: Okra mucilage is a promising natural and safe gel former that can be developed to serve as an alternative to currently used synthetic gel formers for nasal drug delivery.Keywords: Mucilage, Abelmoschus esculentus, Nasal gel, Rizatriptan, Permeation, Mucoadhesion

Amphiphilic glycopolymer nanoparticles as vehicles for nasal delivery of peptides and proteins

Nasal drug delivery system has been a very promising route for delivery of proteins and peptides for the reason that it can avoid degradation in gastrointestinal tract and metabolism by liver enzymes. However, the bioavailability of proteins and peptides is still low due to the rapid clearance of mucociliary. Here, to prolong the residence time of drugs and improve their absorption, we prepared amphiphilic glycopolymer poly(2-lactobionamidoethyl methacrylate-random-3-acrylamidophenylboronic acid) (p(LAMA-r-AAPBA), and the glycopolymer could assemble into the nanoparticles with narrow size distribution. Insulin, as a model drug, was efficiently encapsulated within the nanoparticles, and loading capacity was up to 12%. In vitro study revealed that the insulin release could be controlled by modifying the composition of glycopolymers. Cell viability showed that p(LAMA-r-AAPBA) nanoparticles had good cytocompatibility. Moreover, the mechanism of nanoparticle internalization into Calu-3 cells was a combination mechanism of clathrin-mediated endocytosis and lipid raft/caveolae-mediated endocytosis. Importantly, there was a significant decrease in the blood glucose levels after the nasal administration of p(LAMA-r-AAPBA) nanoparticles to diabetic rats. Therefore, p(LAMA-r-AAPBA) glycopolymers have a potential application as a nasal delivery systems for proteins and peptides.

NASAL ROUTE: A NOVELISTIC APPROACH FOR TARGETED DRUG DELIVERY TO CNS

Drug delivery through nasal route has attracted the interest o f scientific community as it has been potentially explored as an alternative route for the administration of vaccines and biomolecules such as proteins, peptides and non - peptide drugs that are susceptible to enzymatic or acidic degradation and first pass h epatic metabolism. The nasal mucosa is one of the most permeable and highly vascularis ed sites for drug administration ensuring rapid absorption and onset of therapeutic action. Intranasal administration is a non - invasive route for drug delivery, which is widely used for the local treatment of rhinitis or nasal polyposis. Since drugs can be absorbed into the systemic circulation through the nasal mucosa, this route may also be used in a range of acute or chronic conditions requiring considerable systemic ex posure. In addition it minimizes the lag time associated with oral drug delivery and offers non - invasiveness, self medication, patient comfort and patient compliance which are hurdled in intravenous drug therapy. The objective of this revie w is to provide an anatomical, histological and physiological overview of nose, absorption enhancers, barriers related to nasal drug delivery, physicochemic al, biological and formulation related factors affecting nasal drug delivery system and its advantages. It also high lights research approaches on brain targeting through nasal cavity.

Formulation and In Vitro Evaluation of Salbutamol Sulphate In Situ Gelling Nasal Inserts

The aim of this study was to formulate salbutamol sulfate (SS), a model drug, as mucoadhesive in situ gelling inserts having a high potential as nasal drug delivery system bypassing the first-pass metabolism. In situ gelling inserts, each containing 1.4% SS and 2% gel-forming polymer, hydroxypropyl methylcellulose (HPMC), carboxymethylcellulose sodium (CMC Na), sodium alginate (AL), and chitosan (CH) were prepared. The inserts were investigated for their different physicochemical properties. The weight of inserts was 16-27 mg, drug content was 3.9-4.2 mg, thickness ranged between 15 and 28 μm and surface pH was 5-7. Cumulative drug released from the inserts exhibited extended release for more than 10 h following the decreasing order: CH>AL>CMC Na>HPMC. The drug release from CMC Na and AL inserts followed zero-order kinetics while HPMC and CH inserts exhibited non-Fickian diffusion mechanism. The inserts exhibited different water uptake (7-23%) with the smallest values for CH. Differential scanning calorimetry study pointed out possible interaction of SS and oppositely charged anionic polymers (CMC Na and AL). The mucoadhesive in situ gelling inserts exhibited satisfactory mucoadhesive and extended drug release characteristics. The inserts could be used for nasal delivery of SS over about 12 h; bypassing the hepatic first-pass metabolism without potential irritation.

Nasal administration of drugs as a new non-invasive strategy for efficient treatment of multiple sclerosis

We investigated the efficiency of nasal drug administration as a new non-invasive treatment strategy for MS. Glatiramer Acetate (GA) and GA–Cannabidiol (CBD) combination administered in nasal delivery system (NDS) resulted in a statistically significant decrease of clinical scores and inflammatory cytokine expression in experimental autoimmune encephalomyelitis (EAE) mice. Even a suboptimal dose of Prednisolone in NDS was effective in preventing the clinical signs of the disease. Neuron regeneration was observed in the hippocampus of EAE mice treated with GA-CBD in NDS. This work shows that nasal administration improved drug efficiency and stimulates further research for a non-invasive strategy for MS.

Design of Experiments to Optimize an In Vitro Cast to Predict Human Nasal Drug Deposition

Previous studies showed nasal spray in vitro tests cannot predict in vivo deposition, pharmacokinetics, or pharmacodynamics. This challenge makes it difficult to assess deposition achieved with new technologies delivering to the therapeutically beneficial posterior nasal cavity. In this study, we determined best parameters for using a regionally divided nasal cast to predict deposition. Our study used a model suspension and a design of experiments to produce repeatable deposition results that mimic nasal deposition patterns of nasal suspensions from the literature. The seven-section (the nozzle locator, nasal vestibule, front turbinate, rear turbinate, olfactory region, nasopharynx, and throat filter) nylon nasal cast was based on computed tomography images of healthy humans. It was coated with a glycerol/Brij-35 solution to mimic mucus. After assembling and orienting, airflow was applied and nasal spray containing a model suspension was sprayed. After disassembling the cast, drug depositing in each section was assayed by HPLC. The success criteria for optimal settings were based on nine in vivo studies in the literature. The design of experiments included exploratory and half factorial screening experiments to identify variables affecting deposition (angles, airflow, and airflow time), optimization experiments, and then repeatability and reproducibility experiments. We found tilt angle and airflow time after actuation affected deposition the most. The optimized settings were flow rate of 16 L/min, postactuation flow time of 12 sec, a tilt angle of 23°, nozzle angles of 0°, and actuation speed of 5 cm/sec. Neither cast nor operator caused significant variation of results. We determined cast parameters to produce results resembling suspension nasal sprays in the literature. The results were repeatable and unaffected by operator or cast. These nasal spray parameters could be used to assess deposition from new devices or formulations. For human deposition studies using radiolabeled formulations, this cast could show that radiolabel deposition represents drug deposition. Our methods could also be used to optimize settings for other casts.

External Characteristics of Unsteady Spray Atomization from a Nasal Spray Device

The nasal route presents an enormous opportunity to exploit the highly vascularized respiratory airway for systemic drug delivery to provide more rapid onset of therapy and reduced drug degradation compared with conventional oral routes. The dynamics of atomization at low injection pressure is less known as typical spray atomization studies have focused on industrial applications such as fuel injection that are performed at much higher pressure. An experimental test station was designed in house and an alternative method to characterize the external spray is presented. This involved the use of high-speed camera to capture the temporal development of the spray as it is atomized through actuation of the spray device. An image-processing technique based on edge detection was developed to automate processing through the large number of images captured. The results showed that there are three main phases of spray development (prestable, stable, and poststable) that can be correlated by examining the spray width. A comparison with a human nasal cavity is made to put into perspective the dimensions and geometry that the spray atomization produces. This study aimed to extend the current existing set of data to contribute toward a better understanding in nasal spray drug delivery.

Microemulsions for Nasal Drug Delivery Systems: An Overview

Most drugs cannot be given orally because of significant degradation in the GIT or first pass metabolism in the liver. Nasal route for the delivery of some drugs offers an alternative in the pharmaceutical industry. The present review deals with the utility of the nasal route for the delivery of drugs to the brain as a microemulsion system in the treatment of a number of ailments like migraine, epilepsy, and hypertension. The nasal route could be important for drugs that are used in crisis treatments, such as for pain, and for centrally acting drugs where the pathway from nose to brain might provide a faster and more specific therapeutic effect. The purpose of the article is to provide an overview of the concept of microemulsion, selection of surfactant, co-surfactant, oils, formulation of microemulsion, phase diagram study, and evaluation of microemulsion. The review also focuses on the excipients available for formulation of microemulsions for nasal delivery and describes the investigations reported for the various classes of therapeutic agents. The interesting features of microemulsion such as spontaneity of formation, ease of manufacturing, high solubilization capacity and self-preserving properties make them the vehicle of choice for nasal delivery.

Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery

This work describes the preparation and evaluation of mucoadhesive microspheres, using Abelmoschus esculentus polysaccharide as a novel carrier for safe and effective delivery of rizatriptan benzoate into nasal cavity. The polysaccharide was extracted from the fruit of A. esculentus and mucoadhesive microspheres were prepared by emulsification, followed by crosslinking using epichlorohydrin. Prepared microspheres were evaluated for size, morphology, swelling properties, mucoadhesive strength, encapsulation efficiency and drug release. Microspheres were found to release 50% of drug within 15 min and rest of the drug was released within 60 min. The drug release was found to decrease with increasing concentration of polysaccharide. To determine the retention time of the microspheres in the nasal cavity of rabbits, the microspheres were radiolabelled with 99mTc and subjected to gamma scintigraphy. The results showed a significant improvement in the nasal retention of the microspheres as compared to the aqueous solution of radiolabelled free-drug.

Preparation and in vitro characterization of mucoadhesive Norethisterone - egg albumin microspheres for nasal administration.

In this study suitable, smooth, spherical, cross-linked egg albumin microspheres in the size range of 15-40 um loaded with norethisterone were prepared by multiple emulsion (o/w/o) method by the glutarldehyde cross-linking and thermal denaturation technique. Microspheres were prepared by using different drug/polymer ratios. Egg albumin was used as a mucoadhesive polymer in the formulation to increase the residence time of the microspheres on the nasal mucosa. The albumin microspheres were characterized and evaluated with respect to the particle size, production yield, encapsulation efficiency, shape and surface properties, drug polymer interaction, mucoadhesive property and suitability for nasal drug delivery. The in vitro diffusion of NE from the prepared microspheres exhibited the extent of drug release decreased from 95 –60%. The release of the drug has been controlled by swelling control release mechanism. No initial burst release has been recorded except for NE microspheres stabilized using 25% w/v glutarldehyde as cross-linking agent. The drug release from NE microspheres obeys Higuchi diffusion controlled model.