Sheep Nasal Mucosa Research Articles

Direct and enhanced delivery of nanoliposomes of anti schizophrenic agent to the brain through nasal route

The problem of inadequate oral bioavailability of Quetiapine Fumarate, a lipophilic drug used for schizophrenia, due to hepatic metabolism and repulsion by brain barrier was attempted in this study. Combination of two approaches, viz. Quetiapine inclusion into the liposomal carrier for better diffusion and administration through nasal route to avoid hepatic metabolism and barrier elimination was applied. Thin film hydration followed by sonication method was employed in liposome preparation and the formulation was optimized using 32 full factorial design. The number of sonication cycles (X1) of 2min and 80% amplitude and molar ratio of constructional components such as cholesterol to egg phosphatidylcholine (X2) as independent variables and a % of entrapment efficiency (Y1) and cumulative in vitro drug release (Y2) at 6h as dependent variables was selected. Batch F7 prepared by 2 cycles of sonication and 1:3M ratio of cholesterol:egg phosphatidylcholine was optimized as a consequence of substantial entrapment efficiency of 75.63±3.77%, and 99.92±1.88% drug release and 32.33±1.53% drug diffusion, which was optimum among all other batches at 6h. Diffusion study was done for all the batches of liposomal formulation by using sheep nasal mucosa and good amount with better diffusion rate was measured which proved liposomal dispersion a virtuous delivery system for brain drug delivery through nasal route. Results of in vivo, ciliotoxicity and gamma scintigraphy studies on mice supported the above inference.

Development and Characterization of Thermosensitive intranasal Gel Containing Paliperidone Loaded Microspheres

Purpose: The objective of the present investigation was to fabricate a thermosensitive gel containing paliperidone loaded microspheres for the treatment of schizophrenia for brain delivery through nasal route. Incorporation of drug in to microspheres and then in to gel should increase the duration of release and nasal duration time respectively. Material and Method: Ethyl cellulose microspheres containing paliperidone palmitate were prepared by emulsification of ethyl acetate dispersion containing polymer and drug with aqueous external phase containing polysorbate 80. Amount of ethyl cellulose and polysorbate 80 were identified as critical formulation variables influencing the drug release at critical time points, percentage yield and particle size. These factors were studied using 2 factors and 3 level face centered factorial design using Design Expert ® . Drug-excipient compatibility was ascertained using FTIR analysis. The paliperidone microspheres were then incorporated in to Pluronic F127 and HPMC gel having required thermo sensitive and muco adhesive properties. Gel containing microspheres was subjected to Ex vivo permeation study, irritation study using sheep nasal mucosa and pharmacodynamic study (spontaneous motor activity in mice). Results: Microspheres that could sustain the drug release up to 8 hours were developed. Thermoreversible gel having required thermo sensitive and muco adhesive properties was developed. The Ex vivo permeation study and pharm a codynamic study of the drug loaded microsphere containing gel confirmed the release up to 8 hours. The histopathology study showed absence of irritation on sheep nasal mucosa. Conclusion: Paliperidone palmitate loaded microspheres containing gel could prolong and target the drug release to brain and therefore give prolonged and intense action. Key words: Nose to brain delivery, Paliperidone palmitate, Pharmacodynamic activity, Thermoreversible gel, Desirability index.

Nose to Brain Delivery of Midazolam Loaded PLGA Nanoparticles: In Vitro and In Vivo Investigations.

The present study is aimed to develop poly(D, L-lactide-co-glycolic acid) (PLGA) nanoparticles (NP) loaded with midazolam (Mdz) for nose to brain delivery. NP were formulated by nanoprecipitation and characterized for z-average, zeta potential, % drug entrapment and ex vivo drug release. Mdz NP (MNP) were radiolabeled with technetium-99m. Biodistribution and gamma scintigraphic studies were performed on Sprague-Dawley rats following intranasal (i.n) and intravenous (i.v) administration to trace the transport of Mdz for nose-to-brain delivery. MNP showed z-average of 164±4.5nm with polydispersity index 0.099±0.02 and zeta potential of -16.6±2.5mV. Ex vivo drug studies indicated that MNP showed 29±1.2% of permeation upto 4h via sheep nasal mucosa, whereas Mdz suspension (MS) showed drug release of 83±1.2% within 4h. Comparing i.n administration of MNP, MS and i.v administration of MS, scintigraphy imaging and Brain/blood uptake ratios indicated higher brain targeting via i.n administration of MNP. Results indicated that the i.n MNP could be employed as a non invasive mode of delivery system with improved drug entrapment, stability and controlled drug release over a period of time.

Thermoreversible nanoethosomal gel for the intranasal delivery of Eletriptan hydrobromide.

The objective of the current study was to formulate and characterize thermoreversible gel of Eletriptan Hydrobromide for brain targeting via the intranasal route. Ethosomes were prepared by 3(2) factorial design with two independent variables (concentration of soya lecithin and ethanol) and two response variables [percent entrapment efficiency and vesicle size (nm)] using ethanol injection method. Formulated ethosomes were evaluated for preliminary microscopic examination followed by percent drug entrapment efficiency, vesicle size analysis, zeta potential, polydispersibility index and Transmission electron microscopy (TEM). TEM confirms spherical morphology of ethosomes, whereas Malvern zeta sizer confirms that the vesicle size was in the range of 191 ± 6.55-381.3 ± 61.0 nm. Ethosomes were incorporated in gel using poloxamer 407 and carbopol 934 as thermoreversible and mucoadhesive polymers, respectively. Ethosomal gels were evaluated for their pH, viscosity, mucoadhesive strength, in vitro drug release and ex vivo drug permeation through the sheep nasal mucosa. Mucoadhesive strength and pH was found to be 4400 ± 45 to 5500 ± 78.10 dynes/cm(2) and 6.0 ± 0.3 to 6.2 ± 0.1, respectively. In-vitro drug release from the optimized ethosomal gel formulation (G4) was found to be almost 100 % and ex vivo permeation of 4980 µg/ml with a permeability coefficient of 11.94 ± 0.04 × 10(-5) cm/s after 24 h. Histopathological study of the nasal mucosa confirmed non-toxic nature of ethosomal gels. Formulated EH loaded ethosomal thermoreversible gel could serve as the better alternative for the brain targeting via the intranasal route which in turn could subsequently improve its bioavailability.

Brain targeting efficiency of Curcumin loaded mucoadhesive microemulsion through intranasal route

This study was aimed at designing mucoadhesive microemulsion gel to enhance the brain uptake of curcumin through intranasal route. Suitable oil, surfactant and cosurfactant for the development of microemulsion were selected based on maximum curcumin solubility, drug excipients compatibility through FTIR study and non-toxicity to sheep nasal mucosa. Curcumin loaded mucoadhesive microemulsion (CMME) was developed by incorporating polycarbophil as mucoadhesive polymer into Capmul MCM based optimal microemulsion (CME) and was subjected to characterization, stability, mucoadhesion and naso-ciliotoxicity study. Brain uptake of Curcumin via nasal route was studied by performing biodistribution study in Swiss albino rats. CME was found to be transparent, stable and non ciliotoxic with 57.66 nm ± 3.46, −16.28 mV ± 4.11 and 98.08 % ± 1.01 as average globule size, zeta potential and drug content respectively. PdI and TEM study depicted the narrow size distribution of CME. Following single intranasal administration of CMME and CME at dose of 2.86 mg/kg, Maximum Curcumin uptake in the olfactory bulb was more than 11 fold (51.1 ± 2.8) than that of intravenous injection of Curcumin solution (4.4 ± 1.1). AUC ratio of brain tissues to that in plasma obtained after nasal administration of CMME were significantly higher than those after intravenous administration of Curcumin solution. Findings of the present study revealed that optimal CMME and intranasal route may be considered to be promising and an alternative approach for brain targeting of Curcumin.

Stability-Indicating HPTLC Method for Quantitative Estimation of Asenapine Maleate in Pharmaceutical Formulations, Equilibrium Solubility, and ex vivo Diffusion Studies

New high-performance thin layer chromatography (HPTLC) has been successfully developed and validated for quantitative estimation of Asenapine maleate in both marketed tablets and in-house developed formulations (solution, microemulsion, nanoemulsion, and mucoadhesive nanoemulsion) as well as for equilibrium solubility study and ex vivo diffusion study of developed formulation through natural membrane. As suggested by the International Conference on Harmonization, different stress test conditions (alkali, acid, thermal, photolytic, and humidity) were used to degrade Asenapine maleate. The samples produced from this study were utilized to develop a stability indicating HPTLC method. The Asenapine maleate was separated well from degradation products using HPTLC plate; precoated with silica gel G 60 F254 on aluminum sheet as a stationary phase and methanol as a mobile phase. Using densitometric analysis, Asenapine maleate was quantified at 235 nm. The method produced compact band for the drug (Rf = 0.43 + 0.02). The HPTLC method was validated and statistical analysis of the data confirmed the method to be specific, linear, accurate, precise, reproducible, and selective for Asenapine maleate’s analysis. This method was successfully used for assay of Asenapine maleate in both marketed tablets and in-house developed formulations, determining equilibrium solubility in various excipients as well as its ex vivo diffusion study through sheep nasal mucosa from the formulations developed in-house.

PLGA/DPPC/trimethylchitosan spray-dried microparticles for the nasal delivery of ropinirole hydrochloride: in vitro, ex vivo and cytocompatibility assessment

In the present study we investigated polymer-lipid microparticles loaded with ropinirole hydrochloride (RH) for nasal delivery. RH microparticles were further evaluated by means of scanning electron microscopy (SEM), ζ-potential measurements, Fourier-transform infrared spectroscopy (FT-IR), X-ray photoelectron spectroscopy (XPS) and x-ray diffraction (XRD). In vitro release studies were performed in simulated nasal electrolyte solution (SNES) pH5.5 at 35°C. Ex vivo permeation studies were conducted across sheep nasal mucosa. Cytocompatibility was tested in cultured human airway epithelial cells (Calu-3).SEM studies revealed spheroid microparticles in the range of 2.09μm to 2.41μm. The presence of trimethylchitosan (TMC) induced a slight shift towards less negative ζ-potential values. Surface chemistry (XPS) revealed the presence of dipalmitoylphospatidylcholine (DPPC) and poly(lactic-co-glycolic acid) (PLGA) onto microparticles' surface, further corroborating the FT-IR and XRD findings. In vitro release studies showed that the microparticle composition can partly modulate the release of RH. Ex vivo studies demonstrated a 2.35-folded enhancement of RH permeation when RH was co-formulated with TMC of low molecular weight, compared to the control. All formulations tested were found to be non-toxic to cells.The results suggest that polymer-lipid microparticles may be a promising carrier for the nasal delivery of RH.

Development of an optimized hyaluronic acid-based lipidic nanoemulsion co-encapsulating two polyphenols for nose to brain delivery

The development of mucoadhesive lipidic nanoemulsion based on hyaluronic acid, co-encapsulating two polyphenols (resveratrol and curcumin) for the transnasal treatment of neurodegenerative diseases was attempted in the current manuscript. Nanoemulsions were prepared by the spontaneous emulsification method, and were characterized for their particle size, zeta potential, mucoadhesive strength and morphology. The selected formula was tested for its antioxidant potential, in vitro and ex vivo release of the two polyphenols, safety on nasal mucosa and in vivo quantification of the two drugs in rat brains. Its stability was tested by monitoring the change in particle size, zeta potential, drugs' content and antioxidant potential upon storage for 3 months. The optimized hyaluronic acid based nanoemulsion formula displayed a particle size of 115.2 ± 0.15 and a zeta potential of −23.9 ± 1.7. The formula displayed a spherical morphology and significantly higher mucoadhesive strength compared to its non mucoadhesive counterpart. In addition, the nanoemulsion was able to preserve the antioxidant ability of the two polyphenols and protect them from degradation. Diffusion controlled release of the two drugs was achievable till 6 hours, with an ex vivo flux across sheep nasal mucosa of 2.86 and 2.09 µg/cm2hr for resveratrol and curcumin, respectively. Moreover, the mucoadhesive nanoemulsion was safe on nasal mucosa and managed to increase the amounts of the two polypehnols in the brain (about 7 and 9 folds increase in AUC0–7 h for resveratrol and curcumin, respectively). Hyaluronic acid based lipidic nanoemulsion proved itself as a successful carrier enhancing the solubility, stability and brain targetability of polyphenols.

Intranasal microemulsion for targeted nose to brain delivery in neurocysticercosis: Role of docosahexaenoic acid

Intranasal Microemulsions (MEs) for nose to brain delivery of a novel combination of Albendazole sulfoxide (ABZ-SO) and Curcumin (CUR) for Neurocysticercosis (NCC), a brain infection are reported. MEs prepared by simple solution exhibited a globule size <20nm, negative zeta potential and good stability. The docosahexaenoic acid (DHA) ME revealed high and rapid ex vivo permeation of drugs through sheep nasal mucosa. Intranasal DHA ME resulted in high brain concentrations and 10.76 (ABZ-SO) and 3.24 (CUR) fold enhancement in brain area-under-the-curve (AUC) compared to intravenous DHA MEs at the same dose. Direct nose to brain transport (DTP) of >95% was seen for both drugs. High drug targeting efficiency (DTE) to the brain compared to Capmul ME and drug solution (P<0.05) suggested the role of DHA in aiding nose to brain delivery. Histopathology study confirmed no significant changes. High efficacy of ABZ-SO: CUR (100:10ng/mL) DHA ME in vitro on Taenia solium cysts was confirmed by complete ALP inhibition and disintegration of cysts at 96h. Considering that the brain concentration at 24h was 1400±160.1ng/g (ABZ-SO) and 120±35.2ng/g (CUR), the in vitro efficacy seen at a 10 fold lower concentration of the drugs strongly supports the assumption of clinical efficacy. The intranasal DHA ME is a promising delivery system for targeted nose to brain delivery.

Formulation and evaluation of thermoreversible mucoadhesive in-situ gel for intranasal delivery of naratriptan hydrochloride

Intractable migraine presents a significant treatment challenge due to associated throbbing or pulsating headache, which affects one half of the head and lasts from 2 to 72 h. Naratriptan hydrochloride is an approved drug molecule for migraine headaches, but its use is limited due to its poor bioavailability, reoccurrence of migraine and lesser half-life requiring frequent dosing. Therefore, the objective of present study was to formulate a thermoreversible intranasal gel for drug targeting directly to brain via olfactory lobe pathway thereby improving bioavailability. Gels were formulated by using poloxamer 407 as thermoreversible polymer and carbopol 934 as mucoadhesive polymer. Formulated gels were characterized for gelation temperature, gel strength, mucoadhesive strength, viscosity, in-vitro drug release and ex-vivo permeation study using sheep nasal mucosa. In-vitro and ex-vivo drug release studies suggested that the release rate was directly proportional to the concentration of carbopol 934, whereas poloxamer 407 reduced the rate of drug release. Histopathology study of sheep nasal mucosa showed no signs of damage to columnar epithelial cells, confirming non-toxic nature of the formulated gel. Stability studies performed as per ICH guidelines [Q1A (R2)] suggested that the gels were stable.

Formulation of Convenient, Easily Scalable, and Efficient Granisetron HCl Intranasal Droppable Gels.

Deacetylated gellan gum and two sodium alginate polymer types were used each at three concentrations in the suitable range for their sol-gel transition. The prepared nine droppable gels were evaluated in vitro, ex vivo through sheep nasal mucosa, as well as in vivo in comparison to drug solution given intravenously and orally at the same dose. The prepared formulas gelled instantaneously in simulated nasal fluid and the obtained gels sustained their shear thinning and thixotropic behavior up to 48 h. Polymer type and concentration had significant effects on the apparent viscosities and the in vitro release profile of granisetron from the prepared gels. The drug release data best fitted a modified Higuchi equation with initial burst and followed Fickian diffusion mechanism. A 0.5% gellan-gum-based formula sustained the in vitro drug release up to 3 h and enhanced the drug permeation without need for an enhancer. The histopatholgical study revealed the safety of the tested formula. Intranasal delivery recorded double the drug bioavailabilty in comparison to the oral route. It had an absolute bioavailability of 0.6539 and the maximum plasma drug concentration reached after 1.5 h. The developed formula could be promising for the management of chemotherapy-induced nausea and vomiting regarding its improved bioavailability, patient acceptability, and ease of production.

Development of phenytoin intranasal microemulsion for treatment of epilepsy

The objective of the present investigation was to prepare phenytoin microemulsion for intranasal administration by application of experimental design. Phenytoin microemulsion was prepared by water titration method. The concentration of oil (X1), surfactant (X2) and cosurfactant (X3) were selected as independent variables, in a simplex centroid design, from microemulsion region obtained from pseuodoternary phase diagram while the globule size (Y1) and cumulative phenytoin diffused at 60 min (Y2) through sheep nasal mucosa were taken as dependent variables. Mathematical models were generated for the response variables. The validity of the generated equations was established using check point batches. Microemulsion that had a smaller globule size of dispersed phase and high level of % drug diffusion was desirable. The generated mathematical equations were used to identify the desirable zone where all the criteria for the responses were satisfied and an optimum batch was recognized. Ex-vivo study of optimum microemulsion on sheep nasal mucosa shows absence of nasal toxicity. It was found that faster recovery from seizures was obtained in rats treated with intra nasal phenytoin microemulsion in comparison to the rats treated with oral microemulsion and nasal solution. Higher concentration of phenytoin was found in rats treated with intranasal microemulsion in comparison to the rats treated with phenytoin solution administered intraperitoneally. Gamma scintigraphy results also suggested faster availability of drug into brain when microemulsion was administered intranasally.

Nose-To-Brain Delivery of PLGA-Diazepam Nanoparticles.

The objective of the present investigation was to optimize diazepam (Dzp)-loaded poly(lactic-co-glycolic acid) nanoparticles (NP) to achieve delivery in the brain through intranasal administration. Dzp nanoparticles (DNP) were formulated by nanoprecipitation and optimized using Box-Behnken design. The influence of various independent process variables (polymer, surfactant, aqueous to organic (w/o) phase ratio, and drug) on resulting properties of DNP (z-average and drug entrapment) was investigated. Developed DNP showed z-average 148-337 d.nm, polydispersity index 0.04-0.45, drug entrapment 69-92%, and zeta potential in the range of -15 to -29.24 mV. Optimized DNP were further analyzed by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR), ex-vivo drug release, and in-vitro cytotoxicity. Ex-vivo drug release study via sheep nasal mucosa from DNP showed a controlled release of 64.4% for 24 h. 3-[4,5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay performed on Vero cell line showed less toxicity for DNP as compared to Dzp suspension (DS). Gamma scintigraphy and biodistribution study of DNP and DS was performed on Sprague-Dawley rats using technetium-99m-labeled ((99m)Tc) Dzp formulations to investigate the nose-to-brain drug delivery pathway. Brain/blood uptake ratios, drug targeting efficiency, and direct nose-to-brain transport were found to be 1.23-1.45, 258, and 61% for (99m)Tc-DNP (i.n) compared to (99m)Tc-DS (i.n) (0.38-1.06, 125, and 1%). Scintigraphy images showed uptake of Dzp from nose-to-brain, and this observation was in agreement with the biodistribution results. These results suggest that the developed poly(D,L-lactide-co-glycolide) (PLGA) NP could serve as a potential carrier of Dzp for nose-to-brain delivery in outpatient management of status epilepticus.

Development and evaluation of carboplatin-loaded PCL nanoparticles for intranasal delivery

Context: The study was aimed to develop a polymeric nanoparticle formulation of anticancer drug carboplatin using biodegradable polymer polycaprolactone (PCL). The formulation is intended for intranasal administration to treat glioma anticipating improved brain delivery as nasal route possess direct access to brain and nanoparticles have small size to overcome the mucosal and blood–brain barrier.Objective: Development and evaluation of carboplatin-PCL nanoparticles for brain delivery by nasal route.Methodology: Carboplatin-loaded PCL nanoparticles (CPCs) were prepared by double emulsion-solvent evaporation technique and characterized by particle size, zeta potential, entrapment efficiency, scanning electron microscopy and differential scanning calorimetry. The CPCs were assessed for in vitro release kinetics, ex vivo permeation and in situ nasal perfusion. Cytotoxic potential of CPCs in vitro was evaluated on LN229 human glioblastoma cells.Results and discussion: The optimized formulation of carboplatin-PCL nanoparticle CPC-08 with particle size of 311.6 ± 4.7 nm and zeta potential −16.3 ± 3.7 mV exhibited percentage entrapment efficiency of 27.95 ± 4.21. In vitro drug release showed initial burst release followed by slow and continues release indicating biphasic pattern. The ex vivo permeation pattern through sheep nasal mucosa also exhibited a similar release pattern as for in vitro release studies. In situ nasal perfusion studies in Wistar rats demonstrate that CPCs show better nasal absorption than carboplatin solution. In vitro cytotoxicity studies on LN229 cells showed an enhancement in cytotoxicity by CPCs compared to carboplatin alone.Conclusion: CPC-08 effectively improves nasal absorption of carboplatin and can be used for intranasal administration of carboplatin for improved brain delivery.

Brain targeted intranasal delivery of tramadol: comparative study of microemulsion and nanoemulsion

Objective: The present investigation was aimed to develop and compare microemulsion and nanoemulsion for brain targeted intranasal delivery of tramadol to achieve maximum therapeutic efficacy in treatment of episodic and emergency pain.Methods: Tramadol microemulsion (TME) and tramadol nanoemulsion (TNE) were developed and evaluated for physical properties. Ex vivo diffusion and nasal toxicity of TME and TNE were assessed by using sheep nasal mucosa. Biodistribution, pharmacokinetic and pharmacodynamic studies in mice were also performed.Results: Globule sizes of TME and TNE were 16.69 ± 3.21 and 136.3 ± 4.3 nm, respectively. TNE was found be safe with respect to multiple dosing via nasal route. Both TME and TNE were stable during accelerated stability studies. AUC(0→24) in mice brain for TME and TNE was significantly higher as compared with tramadol solution. TME and TNE displayed significantly higher antinociceptive effect for a period of 16 h as compared with tramadol solution.Discussion: TME and TNE were delivered to brain, circumventing BBB in brisk manner, establishing immediately the minimum effective concentration required for therapeutic response. Significant enhancement in antinociceptive effect was observed after intranasal delivery of TME and TNE.Conclusion: Intranasal administration of TME and TNE would be effective in management of episodic and emergency pain treatment.

Surface engineered nanostructured lipid carriers for efficient nose to brain delivery of ondansetron HCl using Delonix regia gum as a natural mucoadhesive polymer

The objective of this investigation was to fabricate ondansetron hydrochloride [OND] loaded mucoadhesive nanostructured lipid carriers [NLCs] for efficient delivery to brain through nasal route. Mucoadhesive NLCs thereby sustaining drug release for longer time in nasal cavity. NLCs were prepared by high pressure homogenization [HPH] technique using glycerol monostearate [GMS]; as solid lipid, Capryol 90; as liquid lipid, soya lecithin; as surfactant and poloxamer 188; as cosurfactant. In the fabrication of NLCs, Delonix regia gum [DRG], isolated from seeds of D. regia belonging to family fabiaceae was used as a mucoadhesive polymer. The NLCs were evaluated for particle size, morphology, drug-entrapment efficiency [%EE], mucoadhesive strength, in vitro drug release, histological examination, ex vivo permeation study, in vivo biodistribution and pharmacokinetic studies in the brain/blood following intravenous [i.v.] and intranasal [i.n.] administration. Particle size, PDI, Zeta potential was observed in the range of 92.28–135nm, 0.32–0.46, and −11.5 to −36.2 respectively. Prepared NLCs achieved thermodynamic stability, control release pattern with minor histopathological changes in sheep nasal mucosa. The significantly [P<0.05] higher values for selected batch was observed, when administered by i.n. route showed higher drug targeting efficiency [506%] and direct transport percentage [97.14%] which confirms the development of promising OND-loaded NLC for efficient nose-to-brain delivery.

COMPARATIVE ASSESSMENT OF CHLORPHENIRAMINE MALEATE PERMEATION THROUGH CELLULOSE ACETATE MEMBRANE AND SHEEP NASAL MUCOSA

The present research work was aimed to develop nasal mucoadhesive microspheres of chlorpheniramine maleate (CPM) &amp; to compare its permeation rate through sheep nasal mucosa and cellulose acetate membrane. The impact of different concentrations of polymer and the dispersion media were evaluated for drug permeation, mucoadhesion, FT-IR and DSC studies. With the increase in polymer concentration, it was observed that the particle size and wall thickness of the microsphere increased; while the in-vitro drug permeation through sheep nasal mucosa significantly decreased when the volume of dispersion media was increased. Histopathological studies show the absence of epithelial cilia destruction. The permeation rate through sheep nasal mucosa was found to be 7.968 µg/hr/cm2, while through cellulose acetate (artificial) membrane showed 8.572 μg/hr/cm2. In conclusion, our results indicate that CPM released from chitosan microspheres penetrate well through sheep nasal mucosa, indicating suitability for nasal administration.

Optimization of artemether-loaded NLC for intranasal delivery using central composite design

The objective of the study was to optimize artemether-loaded nanostructured lipid carriers (ARM-NLC) for intranasal delivery using central composite design. ARM-NLC was prepared by microemulsion method with optimized formulation having particle size of 123.4 nm and zeta potential of −34.4 mV. Differential scanning calorimetry and powder X-ray diffraction studies confirmed that drug existed in amorphous form in NLC formulation. In vitro cytotoxicity assay using SVG p12 cell line and nasal histopathological studies on sheep nasal mucosa indicated the developed formulations were non-toxic and safe for intranasal administration. In vitro release studies revealed that NLC showed sustained release up to 96 h. Ex vivo diffusion studies using sheep nasal mucosa revealed that ARM-NLC had significantly lower flux compared to drug solution (ARM-SOL). Pharmacokinetic and brain uptake studies in Wistar rats showed significantly higher drug concentration in brain in animals treated intranasally (i.n.) with ARM-NLC. Brain to blood ratios for ARM-NLC (i.n.), ARM-SOL (i.n.) and ARM-SOL (i.v.) were 2.619, 1.642 and 0.260, respectively, at 0.5 h indicating direct nose to brain transport of ARM. ARM-NLC showed highest drug targeting efficiency and drug transport percentage of 278.16 and 64.02, respectively, which indicates NLC had better brain targeting efficiency compared to drug solution.

Characterization and In Vitro Evaluation of Freeze-Dried Nasal Insert Composed of Chlorpheniramine Maleate with Ionic and Nonionic Polymer for Intranasal Delivery

In this study, the authors report the fabrication of nasal delivery system, termed nasal insert, and was carried out with ionic and nonionic polymer(s). The data revealed that nonionic polymer has less water uptake and low mucoadhesion time in comparison to the ionic polymers. With ionic polymers, relaxation of entangled polymer from the gel was toward lesser extent, thereby providing sustained release during in vitro release. The SEM images show more compact nature of ionic polymer when compared with nonionic polymer. Histopathology and in vitro permeation study conducted using sheep nasal mucosa showed significantly higher drug permeation from nonionic polymer.

Formulation and optimization of mucoadhesive microemulsion containing mirtazapine for intranasal delivery

Background: Mirtazapine, an antidepressant drug, has absolute bioavailability of only 50% due to high first pass metabolism. Aim: The purpose of this study was to develop and optimize mucoadhesive microemulsion containing mirtazapine for intranasal delivery. Materials and Methods: Based on solubility study, Capmul Medium chain Monoglyceride, Tween 80 and polyethylene glycol (PEG) 400 were selected as oil, surfactant and co surfactant respectively. Microemulsions were prepared using water titration method. 3:1% w/w ratio (Tween 80: PEG 400) was selected for formulation development. The prepared microemulsions were optimized for globule size, zeta potential, % transmittance and polydispersity index. The optimized batch was further characterized for % drug content, conductivity and transmission electron microscopy. Results and Conclusion: All the parameters showed the suitability of microemulsion of mirtazapine for intranasal delivery. Chitosan (0.5% w/w) was used as a polymer for the preparation of mucoadhesive microemulsion to enhance the retention time in the nasal mucosa. Results of nasal toxicity study using excised sheep nasal mucosa showed comparatively no damage to epithelium and so formulation was considered safe for nasal administration. mirtazapine mucoadhesive microemulsion showed the highest percentage of diffusion (57.11 ± 0.710%) after 210 min during in-vitro drug diffusion study through sheep nasal mucosa, followed by mirtazapine microemulsion (46.08 ± 0.674%) and finally by mirtazapine solution (17.63 ± 0.612%).