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Here we fabricated flaxseed oil-based neuronanoemulsions (NNEs) which were further surface-modified with a mucoadhesive polymer, N,N,N‑trimethyl chitosan (TMC) to form mucoadhesive neuronanoemulsions (mNNEs). The NNEs were loaded with high partitioning ropinirole-dextran sulfate (ROPI-DS) nanoplex and fabricated using hot high-pressure homogenization (HPH) technique. NNEs were optimized using Central Composite experimental design. TMC modified mNNE have not been prepared yet for direct nose to brain drug delivery. Here, an objective to provide controlled drug release with prolonged residence on the nasal mucosa for the treatment of Parkinson's disease (PD) is at prime consideration. Enhanced brain targeting through BBB bypass drug delivery, improved therapeutic efficacy through enhanced retention of mNNE formulation over nasal mucosal membrane, reduced dose and frequency of administration, and safety were further expected outcomes of this experiment. The mNNE formulation was subjected to 6 month stability assessment. The mNNE formulation was administered to the Swiss albino mice model via intranasal route and both, the plasma and brain pharmacokinetics were estimated. The in vivo studies performed on mice exhibited high brain targeting efficiency of mNNE formulation through nose to brain delivery via olfactory pathway. The prepared intranasal mNNEs could be on the clinics, if investigated more for behavioral and neurotoxicity studies.

Bicalutamide (BCM) is an anti-androgen drug used to treat prostate cancer. In this study, nanostructured lipid carriers (NLCs) were chosen as a carrier for delivery of BCM using Box-Behnken (BB) design for optimizing various quality attributes such as particle size and entrapment efficiency which is very critical for efficient drug delivery and high therapeutic efficacy. Stability of formulated NLCs was assessed with respect to storage stability, pH stability, hemolysis, protein stability, serum protein stability and accelerated stability. Hot high-pressure homogenizer was utilized for formulation of BCM-loaded NLCs. In BB response surface methodology, total lipid, % liquid lipid and % soya lecithin was selected as independent variable and particle size and %EE as dependent variables. Scanning electron microscopy (SEM) was done for morphological study of NLCs. Differential scanning calorimeter and X-ray diffraction study were used to study crystalline and amorphous behavior. Analysis of design space showed that process was robust with the particle size less than 200 nm and EE up to 78%. Results of stability studies showed stability of carrier in various storage conditions and in different pH condition. From all the above study, it can be concluded that NLCs may be suitable carrier for the delivery of BCM with respect to stability and quality attributes.

Present investigation deals with intranasal delivery of ropinirole hydrochloride (ROPI HCl), loaded in solid lipid nanoparticles (SLNs). Prime objectives of this experiment are avoidance of hepatic first pass metabolism and to improve therapeutic efficacy in the treatment of Parkinson's disease. SLNs were fabricated by emulsification-solvent diffusion technique. A 3(2)-factorial design approach has been employed to assess the influence of two independent variables, namely Pluronic F-68 and stearylamine concentration on particle size, ζ-potential and entrapment efficiency of prepared SLNs. Prepared samples were further evaluated for in vitro drug diffusion, ex vivo drug permeation, histopathological and stability studies. Differential scanning calorimetry analysis revealed the encapsulation of amorphous form of drug into lipid matrix, while scanning electron microscopy studies indicated the spherical shape. Fabricated SLNs had shown no severe signs of damage on integrity of nasal mucosa. Release pattern of prepared drug-loaded sample was best fitted to zero-order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were carried out to compare therapeutic efficacy of prepared nasal formulation against marketed oral formulation. Results of analysis of variance demonstrated the significance of suggested model. Three-dimensional response surface plots and regression equations confirmed the corresponding influence of selected independent variables on measured responses. Our findings suggested the feasibility of investigated system for intranasal administration.

Dextran sulfate sodium (DS) was allowed to interact ionically with ropinirole hydrochloride (ROPI HCl, an anti-Parkinsonian agent) to synthesize self-assembled ROPI-DS nanoplex. The preliminary objective behind ROPI-DS complexation was to enhance the partitioning of ROPI HCl and thereby its encapsulation into nanocarriers and to improve the nasal membrane permeability. Molecular interactions were computed using in silico molecular modeling. Nanoplex were characterized for physicochemical and partitioning behavior. Optimized ROPI-DS nanoplex was further characterized by spectroscopic and thermal analysis, diffraction studies, morphological and histopathological analysis. In summary, ROPI-DS nanoplex represents a promising nanocarrier material for intranasal administration.

In an attempt to increase oral bioavailability and to target intestinal lymphatic transport system, Nimodipine loaded solid lipid nanoparticles (NMD-SLNs) were prepared. Nimodipine (NMD) is highly lipophilic antihypertensive drug having (logP 3.41) and 13% oral bioavailability. NMD-SLNs were prepared with palmitic acid (PA), poloxamer 188 and soya lecithin as a lipid, surfactant and co-surfactant respectively using high pressure homogeniser. A (2(3)) factorial design was employed; three factors such as lipid, surfactant and co-surfactant concentration were used. Parameters investigated includes particle size, polydispersity index (PDI), zeta potential, drug entrapment efficiency (EE %), drug loading efficiency (LE %), in vitro drug release of the SLNs. Optimised SLNs (F8) had particle size of 116±21 nm, zeta potential of -10±(-4.8) mV, EE of 93.66±9.72% and cumulative drug release of 87.52±2.54% in 10 h. The pharmacokinetic study of optimised SLNs conducted in male Albino Wistar rats showed 2.08-fold increase in relative bioavailability than that of NMD solution, when administered orally. Differential scanning calorimetry study revealed absence of any chemical interaction between NMD and PA while SEM study confirmed the non spherical shape of optimised SLNs. Accelerated stability studies showed that there was no significant change in the mean particle size and PDI after storage at 25±2°C/60±5% RH for the period of three months. Due to enhanced bioavailability, these NMD-SLNs are considered to be promising vehicles for oral delivery.

The objective of present work was to enhance the solubility and bioavailability of poorly aqueous soluble drug Irbesartan (IBS). The solid dispersions were prepared by spray drying method using low viscosity grade HPMC E5LV. Prepared solid dispersions were characterized by dissolution study, fourier transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and X-ray diffraction studies (XRD). Results of the SEM, DSC and XRD study showed the conversion of crystalline form of IBS to amorphous form. The dissolution rate was remarkably increased in case of solid dispersion compared to pure IBS. Solubility and stability of solid dispersion was increased due to surfactant and wetting property, slowing devitrification and having anti-plasticization effect of HPMC E5LV. In vivo studies were performed in healthy rabbits (New Zealand grey) and compared with plain IBS. Solid dispersions showed increase in relative bioavailability than the plain IBS suspension. In conclusion, the prepared solid dispersions showed remarkable increase in solubility, dissolution rate and hence bioavailability of poorly water soluble drug Irbesartan.

Objectives The objective of the present investigation was to enhance the solubility and dissolution rate of atorvastatin calcium (ATR) by a solid dispersion technique using poly(ethylene glycol) 6000 (PEG 6000). Methods Microwave energy was used to prepare an enhanced release dosage form of the poorly water soluble drug ATR with PEG 6000 as a hydrophilic carrier. After the microwave treatment, the drug and hydrophilic polymer get fused together to form a solid dispersion. An in-vivo study was performed to determine the lipid-lowering efficacy (cholesterol, high density lipoprotein and triglyceride) of the solid dispersions using a Triton-induced hypercholesterolemia model in rats. Key findings An increase in the solubility of ATR was observed with increasing concentration of PEG 6000. The optimized ratio for preparation of solid dispersions of ATR with PEG 6000 was 1 : 12 w/w by conventional fusion and the microwave induced fusion method. Differential scanning calorimetry and powder X-ray diffraction studies of the solid dispersions confirmed the conversion of some crystalline ATR into the amorphous form. Scanning electron microscopy images also showed conversion of some crystalline ATR into the amorphous form. The in-vitro study showed that solid dispersions increased the solubility and dissolution rate of ATR, and thus may improve its bioavailability compared with plain ATR. The solid dispersion formulation prepared by the microwave induced fusion method significantly (P < 0.05) reduced serum lipid levels in phases I and II (18 h and 24 h) of the Triton test compared with plain ATR. Conclusions The microwave induced fusion method could be considered as a simple, efficient method to prepare solid dispersions of ATR with significant enhancement of the in-vitro dissolution rate as well as in-vivo activity.

The aim of the present study was to prepare mucoadhesive multiparticulate system for oral drug delivery using ionic gelation technique. Microspheres of different mucoadhesive polymers including hydroxypropyl methylcellulose (HPMC) K15M and carbopol 971P were prepared. In this technique cross linking of sodium alginate with calcium chloride was done which retarded the release of drug from the mucoadhesive polymer. In the present work atenolol was used as model drug. Interaction studies performed using FT-IR spectroscopy revealed that there was no drug to polymer interactions. Multiparticulates so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 23-74%. Particle size of the multiparticulates as determined by the scanning electron microscopic analysis (SEM) studies was found to be between 561-831 microm. The prepared formulations also exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique. The multiparticulate so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation. Atenolol release from the multiparticulate system was regulated and extended until 12 h and exhibited a non-Fickian anomalous transport from the swellable microspheres, as evident from the release rate exponent values which varied between 0.569-0.622. The stability studies performed on the optimized batch at 40 degrees C/75% RH for 90 d indicated no significant change in the physicochemical properties. In vivo radioimaging studies in rabbits showed the residence of mucoadhesive microspheres for 6-8 h in upper part of gastrointestinal tract (GIT).

The objective of this study was to formulate and evaluate the pluronic lecithin organogel containing flurbiprofen for topical application. Different formulations of pluronic lecithin organogels were prepared by using pluronic F127, lecithin, flurbiprofen, isopropyl palmitate, water, sorbic acid, and potassium sorbate. To study the in vitro potential of these formulations, permeation studies were performed with Keshary-Chien diffusion cells. The results of the in vitro permeation studies found that release of flurbiprofen from dialysis membrane-70 was more than excised dorsal rat skin. Gelation temperature study was carried out to determine the temperature where sol-gel transformation takes place. The viscosities of different formulations were determined by using Brookfield Viscometer at 25°C, the viscosity of formulations increases as the lecithin concentration increases. Also the formulations were tested for appearance and feel psychorheologically, pH, and drug content. Interactions between the components of the gel have been investigated by differential scanning calorimetry and X-ray powder diffractometry. The optimized formulation subjected to differential scanning calorimetry shows no drug-polymer interaction. To investigate the in vivo performance of the formulations, a carrageenan-induced rat paw edema model and skin irritation study was used. The stability studies and freeze-thaw thermal cyclic test were carried out, showing no phase separation of gel, and representing gel stability. Statistical analysis of the data of animal study (anti-inflammatory activity) was done by using one way analysis of variance (ANOVA) followed by Dunnett's test. The formulation shows a statistically significant anti-inflammatory activity and is non-irritant to skin.

Here we report fabrication and evaluation of novel surface modified polymer-lipid hybrid nanoparticles (PLN) as robust carriers for intranasal delivery of ropinirole hydrochloride (ROPI HCl). Sustained release, avoidance of hepatic first pass metabolism, and improved therapeutic efficacy are the major objectives of this experiment. PLN were fabricated by emulsification-solvent diffusion technique and evaluated for physicochemical parameters, in vitro mucoadhesion, in vitro diffusion, ex vivo permeation, mucosal toxicity and stability studies. Box-Behnken experimental design approach has been employed to assess the influence of two independent variables, viz. surfactant (Pluronic F-68) and charge modifier (stearylamine) concentration on particle size, ζ-potential and entrapment efficiency of prepared PLN. Numerical optimization techniques were used for selecting optimized formulation sample, further confirmed by three dimensional response surface plots and regression equations. Results of ANOVA demonstrated the significance of suggested models. DSC and SEM analysis revealed the encapsulation of amorphous form of drug into PLN system, and spherical shape. PLN formulation had shown good retention with no severe signs of damage on integrity of nasal mucosa. Release pattern of drug-loaded sample was best fitted to zero order kinetic model with non-Fickian super case II diffusion mechanism. In vivo pharmacodynamic studies were executed to compare therapeutic efficacy of prepared nasal PLN formulation against marketed oral formulation of same drug. In summary, the PLN could be potentially used as safe and stable carrier for intranasal delivery of ROPI HCl, especially in treatment of Parkinson's disease.

The present investigation deals with the development and statistical optimization of solid lipid nanoparticles (SLNs) of ondansetron HCl (OND) for intranasal (i.n.) delivery. SLNs were prepared using the solvent diffusion technique and a 2(3) factorial design. The concentrations of lipid, surfactant and cosurfactant were independent variables in this design, whereas, particle size and entrapment efficiency (EE) were dependent variables. The particle size of the SLNs was found to be 320-498 nm, and the EE was between 32.89 and 56.56 %. The influence of the lipid, surfactant and cosurfactant on the particle size and EE was studied. A histological study revealed no adverse response of SLNs on sheep nasal mucosa. Transmission electron microscopic analysis showed spherical shape particles. Differential scanning calorimetry and X-ray diffraction studies indicated that the drug was completely encapsulated in a lipid matrix. In vitro drug release studies carried out in phosphate buffer (pH 6.6) indicated that the drug transport was of Fickian type. Gamma scintigraphic imaging in rabbits after i.n. administration showed rapid localization of the drug in the brain. Hence, OND SLNs is a promising nasal delivery system for rapid and direct nose-to-brain delivery.

In the present study, tramadol HCl microspheres were designed in order to accomplish rapid delivery of drug to the brain. For this purpose, lower viscosity grade HPMC (E15) was chosen as mucoadhesive polymer and used at different drug/polymer ratios in the microspheres formulations. The spray-dried microspheres were evaluated with respect to the production yield, incorporation efficiency, particle size, mucoadhesive property, in vitro drug release, histopathological study, and radio imaging study in rabbits. DSC and XRD study showed molecular dispersion and conversion of the drug into amorphous form. Size and surface morphology of microspheres was analyzed by SEM and found to be spherical in shape with smooth surface. It was found that the particle size, swelling ability, and incorporation efficiency of microspheres increase with increasing drug-to-polymer ratio. Microspheres show adequate mucoadhesion and do not have any destructive effect on nasal mucosa. In vitro drug release of optimized formulation was found to be 94% after 90 min. The radio imaging study indicated localization of drug in the brain. Hence, tramadol HCl microspheres based on a HPMC E15 may be a promising nasal delivery system for CNS targeting.

The present investigation deals with the development of a pH and time-dependent press-coated pulsatile drug delivery system for delivering drugs into the colon. The system consists of a drug containing core, coated by a combination of natural polymer Delonix regia gum (DRG) and hydroxypropyl methylcellulose (HPMC K4M) in various proportions, which controls the onset of release. The whole system was coated with methacrylic acid copolymers, which not only prevents the drug release in the stomach, but also prolongs the lag time. Tramadol HCl was used as a model drug and varying combinations of DRG and HPMC K4M were used to achieve the desired lag time before rapid and complete release of the drug in the colon. It was observed that the lag time depends on the coating ratio of DRG to HPMC and also on press coating weight. Drug release was found to be increased by 15-30% in the presence of colonic microbial flora. The results showed the capability of the system in achieving pulsatile release for a programmable period of time and pH-dependent release to attain colon-targeted delivery.

The aim of the present study was to prepare mucoadhesive multiparticulate system for oral drug delivery using ionic gelation technique. Microspheres composed of various mucoadhesive polymers including HPMC of various grades like K4M, K15M, K100M, E50LV, Carbopol of grades 971P, 974P and polycarbophil were prepared. In this technique cross linking of sodium alginate with calcium chloride was done which retarded the release of drug from the mucoadhesive polymer. In the present work Metoprolol tararate was used as a model drug. Interaction studies performed using FTIR spectroscopy revealed that there was no drug to polymer interactions. The preliminary mucoadhesive strength studies performed for various polymers using rotating cylindrical method showed that HPMC had greater mucoadhesive properties than carbopol and polycarbophil. Microspheres so prepared were discrete, bulky, free flowing and showed an average encapsulation efficiency ranging from 50-60%. Particle size of the microspheres, as determined by the optical microscopy was found to be between 400-650 microm. The prepared formulations also exhibited a good mucoadhesive strength which was determined in in vitro conditions through falling film technique and was compared with ex vivo studies. The microspheres so prepared also exhibited a good swelling index which confirmed the strong mucoadhesive property of the formulation. Metoprolol release from the multiparticulate system was regulated and extended until 12 hours and exhibited a non fickian drug release kinetics approaching to zero order, as evident from the release rate exponent values which varied between 0.57 to 0.73. The stability studies performed on the optimized batches at 40 degrees C /75% RH for 90 days indicated no significant change in the physicochemical properties.