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Starch is used as a key polymer in pharmaceutical industries since long back for various purposes such as binder, disintegrating agent, bulking agent, film former and many more. But as per the purpose of dosage forms it’s used get changed. Currently scientists are more focused on controlled and sustained release dosage forms. Since, native starch does not meet up the demand of controlled or sustained release, so there is need of modifying the polymer as per dosage form requirement. Modification of starch can be done by physical, chemical, enzymatic, and genetic method. Among all, the current article is focusing on chemical modification of starch, especially the acetylation. Acetylation of starch can be done using different acetylating agent such as acetic anhydride (AA), and glacial acetic acid etc. and sodium hydroxide (NaOH), pyridine and sulphuric acid etc as a catalyst. The native structure of starch can be less efficient, since its functional properties are less stable to process condition such as high temperature, shear stress and exposure to acidic media, which decreases its use in industrial application. Acetylated starches facilitate higher stability and resistance to retrogradation or crystallization, enhanced granular size, swelling power, and water absorption capacity, which provides good flow and compression properties. It reduces the pasting temperature and solubility. It makes the acetylated starch as a good candidate for customizing the overall performance of native starch, which may be used as the controlled release or sustained release polymer in pharmaceutical dosage form.

Aim: The work mainly focuses on developing a robust UV-Visible spectroscopic method for qualitative and quantitative analysis of thymoquinone and this will open to many possibilities in exploiting the wonders of this bioactive molecule. Study Design: UV-vis Spectrophotometric method development for thymoquinone. Place and Duration of Study: Department of Pharmaceutics, Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University Campus, Nagpur, India. Methodology: To find out λmax and validate the developed method using Double beam UV – visible spectrophotometer module (JASCO V-630). Results: The thymoquinone was found to be soluble in methanol. The absorption maximum (λmax) was found to be 252 nm. The good linearity was found to be within concentration range of 2-10 μg/ml with correlation coefficient (r2) >0.99 and regression equation of the curve was found to be y = 0.0173x − 0.0394 at 252 nm. The precision (intra-day and inter-day) data represents good reproducibility with % RSD lower than 2.0% which assured that method is précised. Mean recovery value at different concentrations was found to be higher than 90%, indicates accuracy of the method. LOD and LOQ for thymoquinone were reported and were found to be 0.016 μg/ml and 0.0531μg/ ml 252 nm. Conclusion: The developed method was found to be simple, specific, economic, reliable, accurate, precise, and reproducible used as a quality control tool for analysis of pure thymoquinone and thymoquinone in formulations.

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.

Present work demonstrated the influence of novel amphiphilic carrier Soluplus® on the solubility and oral bioavailability of Morin hydrate (MOR). Spray-dried solid dispersions (SSD) were developed using the design of experiment (DoE). Saturation solubility study of the optimized formulation SSD F(7) showed many fold increment in the solubility with acceptable aqueous stability. In vitro drug diffusion kinetics suggested Weibull model to be the best fit. In vitro cytotoxicity assay revealed a significant increase in the anticancer potential compared to innate MOR. Furthermore, SSD F(7) showed 2.27-fold enhancement in the relative bioavailability as compared to MOR. BCS: biopharmaceutical classification system; MOR: Morin hydrate; SD: solid dispersion; SSD: spray dried solid dispersion; PM: physical mixture; CCD: central composite design; PSD: particle size distribution; PDI: polydispersity index; SEM: scanning electron microscopy; XRD: X-ray diffraction; DSC: differential scanning calorimetry; TGA: thermal gravimetric analysis; DTA: differential thermal analysis; DTG: derivative thermogravimetry; Tg: glass transition temperature; API: active pharmaceutical ingredient; P-gp: permeability glycoprotein; SRB: sulforhodamine B; ADR: adriamycin; DoE: design of experiment

N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of chitosan (CHT), outperformed the well-known solubility issues raised by CHT. The excellent properties offered by TMC provide it a significant edge for nanoparticle (NP) formation over other nanocarrier materials. Recently, TMC NPs have been applied to various fields like pharmaceutical, biomedical, biomaterials, and biotechnological field. The aim of this review is, therefore, to bring the TMC into the limelight so as to appraise it as an attractive functional polymer for nanomedicine applications which is facing oversight, at present, by regulatory agencies and manufacturers. The versatility of surface-tailoring, the capability of further chemical modifications, and the feasibility of ligand-conjugations in TMC polymer will further assist the scientists for reaching new dimensions in the nano-assembly of novel structures based on TMC.

Present work demonstrates the impact of sulfobutyl ether-β-cyclodextrin (SBE-β-CD, Captisol ® ) complexation on the solubility, dissolution and pH stability of the poorly soluble polyphenol chrysin (CHR) by freeze-drying technique. Phase solubility indicated the 1:1 stoichiometry. FTIR, DSC, PXRD, and SEM analysis confirmed the formation of inclusion complex. Moreover, 1 H NMR studies illustrated that the possible inclusion mode was through A-ring of the CHR which was further confirmed by molecular modelling. In addition, CHR/SBE-β-CD complex exhibited ∼108 times higher solubility and faster dissolution compared to CHR. The pH stability profile exhibited the protective effect of SBE-β-CD on the CHR at simulated pH. Also, in vitro cytotoxicity assay revealed an appreciable improvement in the anticancer activity of complex compared to free CHR, on MCF-7 and HeLa cell lines validating its superiority as a carrier.

Here we report the development of tristearin-based nanostructured-lipid carriers (NLCs) which were further surface-modified with mucoadhesive N,N,N-trimethyl chitosan (TMC) to form mucoadhesive nanostructured-lipid carriers (mNLCs). The NLCs were loaded with high partitioning ropinirole-dextran sulphate (ROPI-DS) nanoplex. NLCs were optimised using Box-Behnken experimental design. Obtaining controlled drug release with prolonged residence on the nasal mucosa for treating Parkinson’s disease (PD) is a major objective of the present investigation. Enhanced brain targetability and improved therapeutic efficacy are the additional objective of this study. Lyophilised NLCs and mNLCs were characterised in solid state by FTIR, DSC, XRD, and HR-TEM analysis. The bioadhesive strength of mNLCs was observed to be 13.3-folds greater compared to NLCs. Plasma and brain pharmacokinetic studies in mice model demonstrated the potential of mNLCs in nose-to-brain drug delivery via olfactory pathway. If investigated for behavioural and neurotoxicity studies clinically, a commercial formulation for patient looks feasible.

The blood–brain barrier (BBB) is the major obstacle in the effective delivery of neurotherapeutics to the brain microenvironments. The dense membrane hampers the access of many of the therapeutic drugs to reach to the brain regions in sufficient concentrations, leading to poor patient compliance and discontinuation of the neurotherapy. A direct transport of neurotherapeutics from nose to brain regions along the well-known olfactory and trigeminal nerve pathways seems to be an effective strategy to overcome the BBB, and we propose the direct nose-to-brain drug delivery as an effective strategy for safe and noninvasive administration of the neurotherapeutics. Existence of direct entry point from nose to brain encourages the scientists to explore the opportunities in optimizing therapy of neuroailments. This chapter highlights the diagnosis and therapy of major neurodegenerative disorders (NDs) and developments in the nanotechnological areas for effectively delivering the neurotherapeutics to target the neuronal regions via direct nose-to-brain transport.

The polyelectrolyte complexes (PECs) are versatile formulations formed by electrostatic interactions between oppositely charged biopolymers. PECs have been investigated widely by the researchers to explore the virtues of this formulation viz. high biocompatibility, excellent biodegradability, low toxicity, cost-effective, environment-friendly, and energy-efficient production. The prime object of the present review is to present the prominent features of PECs including mechanism of PEC formation, structural models of PECs, interactions involved in PEC formation, steps involved in PEC fabrication, factors affecting the formation of PECs and applications of PECs. The patents pertaining to PECs have briefly been tabulated as well.

The near future of drug delivery system would lie in the search for a versatile and innocuous biomaterial, based mostly on natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose (hydrophilic polysaccharide) consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is gifted with distinct mucoadhesive and in situ gelling properties which rated XG as an attractive, and functional polymer for numerous drug delivery applications. On these grounds, the present chapter is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface tailoring, the flexibility of chemical modification, and the possibility as ligand conjugations grant XG an extraordinary attention in the scientific community. The authors are assured that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the coming years, if sufficiently investigated and promising outcomes are obtained in human subjects.

The brain-blood ratio is an important model correlating the brain-targeting ability of neurotherapeutics with the CNS pharmacokinetics, which need to be presented before the scientific community for exploration of its scientific worth. The purpose of this article is to bring this key concept and its precise discussion to the attention of the researchers.Three major points are discussed herein: First, the significance of brain-blood ratio with respect to investigational neurotherapeutics, and carrier systems and correlation of its research findings with the brain targeting efficiency. Second, the various factors influencing the brain-blood ratio. Third, the various strategies for enhancing the brain-blood ratio. In addition, the benchmark criteria for CNS-likeness of drug molecules and the correlation of brain-blood ratio with brain targeting ability of neurotherapeutics have been tabulated.The brain-blood ratio (also referred to as the brain-plasma ratio) represents one of the tools available today for estimation of CNS pharmacokinetics. It is preferred over other complicated techniques (in situ brain perfusion and microdialysis) due to its ease of use and practicality. We are optimistic that the brain-blood ratio offers an excellent way of evaluating brain-targeting efficiency of neurotherapeutics effectively. In our opinion, it is a very fundamental aspect of brain bioavailability and needs to be presented in a precise way.

The near future of drug delivery system would lie in the search of a versatile and innocuous material, based mostly on the natural resources. The tamarind seed xyloglucan (XG) is a natural neutral hemicellulose and a hydrophilic polysaccharide consisting of a main chain of glucan backbone with xylose and galactose side chains. XG is endowed with idiosyncratic mucoadhesive and in situ gelling properties which rated XG as an attractive, functional polymer for numerous drug delivery applications. In milieu of this, the present review is designed to underline the plausible potential of XG or XG-based systems in drug delivery. The feasibility of surface-tailoring, the flexibility of chemical-modification, and the possibility as ligand-conjugations grant XG an extraordinary consideration in the scientific territory. The authors are hopeful that the versatility of XG would meet the expectations of regulatory authorities and the XG-based products will serve the therapeutic needs of the community in the future, if sufficiently investigated and promising outcomes are obtained in human subjects.

Nanotechnology has the potential to revolutionize diagnosis and therapy. Advances in protein engineering and material science have contributed to novel nanoscale targeting approaches that may bring new hope to patients. Recent developments in nanotechnology offer opportunities to significantly transform therapeutics. This technology has enabled the manipulation of the biological and physicochemical properties of nanomaterials to facilitate more efficient target-specific drug therapy. Engineered nanoparticles are an important tool to realize a number of these applications. Generally, particles having size ≤100 nm can only be used for medical purpose. Recent years have witnessed unprecedented growth of research and applications in the area of nanoscience and nanotechnology. There is an increasing optimism that nanotechnology, as applied to medicine, will bring significant advances in the diagnosis and treatment of disease.

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.

The aim of present investigation was formulation and in-vitro evaluation of in situ gel for the nasal delivery of zolmitriptan. The in situ gel was prepared by temperature induced gelation technique using Pluronic with mucoadhesive polymer hydroxy propyl methyl cellulose K4 M in different ratios. The in situ gels so prepared were characterized and from the evaluation studies, batch PH2 was optimized and further subjected for stability studies at 30±2°C and 60±5% RH for 90 days. These formulations retained good stability at accelerated conditions and also did not show any remarkable damage to nasal mucosa in histopathological study. Owing to these properties it can be used as an effective delivery system for the nasal route.

The objective of present study was to modify the surface of Poly(D,L-lactide-co-glycolide acid) (PLGA) nanoparticles (NPs) with chitosan to enhance the mucoadhesive potential of carrier system. Grafting of chitosan on PLGA surface was carried out via amide bond formation mediated by carbodiimide and confirmed by FTIR spectroscopy. Self-assembled PLGA NPs containing chlorpromazine hydrochloride were fabricated by 23 factorial design. The improved mucoadhesive potential was confirmed by several tests including in vitro mucoadhesion study. Ex vivo permeation was satisfactory. Histopathological study on sheep nasal mucosa revealed safe mucoadhesion. They were also found to be robust on accelerated stability study.

The objective of the present work was to enhance the solubility and dissolution of practically water-insoluble drug raloxifene HCl (RLX), for the same two approaches that were used. In the first approach, drug was kneaded with hydroxypropyl-β-cyclodextrin (HPβCD), and in the second one drug was cogrinded with modified guar gum (MGG). The drug-cyclodextrin complex and drug-MGG cogrind mixtures were characterized by differential scanning calorimetry, X-ray diffraction studies, scanning electron microscopy, and Fourier transform infrared spectroscopy. The solubility and dissolution study reveals that solubility and dissolution rate of RLX remarkably increased in both methods. It was concluded that the prepared inclusion complex showed a remarkable increase in solubility and dissolution of poorly water-soluble drug raloxifene. In the cogrinding mixture, a natural modified gum is used as a surfactant and enhances the solubility and dissolution of RLX without requiring addition of organic solvent or high temperature for its preparation; thus, process is less cumbersome and cost effective. But when both methods were compared; HPβCD complexation method showed significant enhancement of drug solubility.

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 the era of nanoparticulate controlled and site specific drug delivery systems, use of solid lipids to produce first generation lipid nanoparticles, solid lipid nanoparticles (SLN), became a revolutionary approach in the early nineties. The present review is designed to provide an insight into how SLN are finding a niche as promising nanovectors and forms a sound basis to troubleshoot the existing problems associated with traditional systems. Herein, authors had tried to highlight the frontline aspects prominent to SLN. An updated list of lipids, advanced forms of SLN, methods of preparation, characterization parameters, and various routes of administration of SLN are explored in-depth. Stability, toxicity, stealthing, targeting efficiency and other prospectives of SLN are also discussed in detail. The present discussion embodies the potential of SLN, now being looked up by various research groups around the world for their utility in the core areas of pharmaceutical sciences, thereby urging pharmaceutical industries to foster their scale-up.

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).

An objective of the present study was to develop alginate/hydroxypropyl methylcellulose (HPMC) based floating-mucoadhesive beads of clarithromycin to provide prolonged contact time of antibiotic to treat stomach ulcer. Floating-mucoadhesive beads were prepared and characterized for in vitro performance followed by investigation of ex vivo study in albino-wistar rats. Beads were prepared by ionic gelation technique where calcium chloride used as gelating agent and incorporated liquid paraffin for floating of the beads. Prepared beads were evaluated extensively for particle size, drug entrapment; swelling and surface morphology by using scanning electron microscopy. X-ray radioimaging study in rabbits, in vitro mucoadhesion using rat stomach mucosal membrane and in vitro drug release studies were carried out. Ex vivo performance of alginate-HPMC beads were studied using albino rats in comparison to simple alginate-calcium beads. Alginate-HPMC beads may be suitable floating-muco-adhesive drug delivery system for delivering clarithromycin to treat stomach ulcers.

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.

The objective of this study was to develop a floating, pulsatile, multiparticulate drug delivery system intended for chronopharmacotherapy of arthritis. The floating pulsatile drug delivery has the advantage that a drug can be released in the upper gastrointestinal tract after a definite time period of no drug release, i.e. lag time. Cross-linked beads were prepared using low methoxylated pectin (LM104AS), sodium alginate, and low methoxylated pectin (LM104AS) along with sodium alginate by acid- base reaction during ionotropic gelation. Beads were dried in oven at 50 degrees C for 4 h. Aceclofenac was used as a model drug for encapsulation. Drug loaded multiparticulates were subjected to various characterization and evaluation parameters like entrapment efficiency, surface topography, size analysis and in vitro release study. It was found that calcium pectinate beads show maximum drug entrapment. Hence, pectin containing formulation was further studied for buoyancy, DSC and radio imaging study. Drug release study was performed in acidic environment using pH 1.2 buffer solution for 6 h and then at 7.4 pH for 60 min. The total drug release ranges from 5-10% and 90-94% in acidic and basic media, respectively.

Although chitosan (CHT, a linear cationic polysaccharide) is biodegradable, biocompatible, non-toxic, and mucoadhesive in nature, the low solubility of CHT in aqueous and alkaline media limits its applicability in pharmaceutical and biomedical field. This necessitate the introduction of new chemically-modified derivatives of CHT those can surmount the solubility barrier. Herein, N,N,N-trimethyl chitosan (TMC), a quaternized hydrophilic derivative of CHT, was synthesized by two-step reductive methylation of CHT and characterized for 1H NMR and zeta potential measurements. Polyelectrolyte complexes (PECs) based on TMC and dextran sulfate (DS) were prepared via ionic interactions between charged functional groups of former polysaccharides at different pH conditions (pH 5, 8, 10, and 12) and characterized for physicochemical (particle size and zeta potential) and solid- state characterizations (HR-TEM, SEM, FTIR, TGA and XRD). At alkaline pH conditions, the participant polymer chains (TMC and DS) are sufficiently close to form more stable PECs. The release efficiency was assessed after loading a model drug into optimized PEC formulation. Data indicated that the PECs fabricated at alkaline pH presents a reliable formulation for pharmaceutical and biomedical applications.

In an experiment to explore the bioadhesion, biocompatibility, and membrane permeation properties, the controlled synthesis of N,N,N-trimethyl chitosan (TMC) was carried out by two-step reductive methylation of chitosan (CHT). Methylation was confirmed by (1)H NMR (δ=3.1 ppm) and FTIR analysis (CH stretch at 1,485 cm(-1)). The TMC was further characterized by DSC, TGA, XRD, HR-TEM, SEM, and elemental analysis. Findings revealed improved solubility, enhanced viscosity, increased swelling index and higher molecular weight of TMC over CHT. Comparative evaluation validated increased bioadhesion potential, and improved ex vivo biocompatibility of TMC compared to CHT. Increased bioadhesion of TMC NPs over CHT NPs can be attributed to the strong electrostatic interactions between cationic amino groups with anionic sialic and sulfonic acid moieties contained in the mucin of the nasal mucus. Ex vivo biocompatibility studies suggested that the NP formulations of both biopolymers were biocompatible and could be applied safely on the nasal epithelium. Ex vivo permeation studies executed on excised cattle nasal mucosa illustrated improved permeability of TMC NPs over CHT NPs. In the author's opinion, two-step reductive methylation of CHT could be an attractive strategy to improve its solubility, bioadhesion, and permeation characteristics without affecting biocompatibility across the mucosal surfaces.

Nose to brain delivery of neurotherapeutics have been tried by several researchers to explore the virtues of this route viz. circumvention of BBB, avoidance of hepatic metabolism, practicality, safety, ease of administration and non-invasiveness. Nanoparticle (NP) therapeutics is an emerging modality for the treatment of Parkinson's disease (PD) as it offers targeted delivery and enhances the therapeutic efficacy and/or bioavailability of neurotherapeutics. This review presents a concise incursion into the nanomedicines suitable for PD therapy delivered via naso-brain transport. Clinical signs of PD, its pathophysiology, specific genetic determinants, diagnosis and therapy involved have been hashed out. Properties of brain-targeting NPs, transport efficacy and various nanocarriers developed so far also been furnished. In our opinion, nanotechnology-enabled naso-brain drug delivery is an excellent means of delivering neurotherapeutics and is a promising avenue for researchers to develop new formulations for the effective management of PD.

The blood-brain barrier (BBB) represents a stringent barrier for delivery of neurotherapeutics in vivo. An attempt to overcome this barrier is represented by the direct transport of drugs from the nose to the brain along the olfactory and trigeminal nerve pathways. These nerve pathways initiate in the nasal cavity at olfactory neuroepithelium and terminate in the brain. An enormous range of neurotherapeutics, both macromolecules and low molecular weight drugs, can be delivered to the central nervous system (CNS) via this route.Present review highlights the literature on the anatomy-physiology of the nasal cavity, pathways and mechanisms of neurotherapeutic transport across nasal epithelium and their biofate and various strategies to enhance direct nose to brain drug delivery. The authors also emphasize a variety of drug molecules and carrier systems delivered via this route for treating CNS disorders. Patents related to direct nose to brain drug delivery systems have also been listed.Direct nose to brain drug delivery system is a practical, safe, non-invasive and convenient form of formulation strategy and could be viewed as an excellent alternative approach to conventional dosage forms. Existence of a direct transport route from the nasal cavity to the brain, bypassing the BBB, would offer an exciting mode of delivering neurotherapeutic agents.

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.

This investigation deals with the intranasal delivery of Valsartan, encapsulated in HPMC-based spray-dried mucoadhesive microspheres, with an aim to provide rapid absorption and quick onset of action for treating hypertension. A 2³-factorial design has been employed for the assessment of influence of three independent variables, namely inlet temperature, feed-flow rate and drug-polymer ratio on production yield, particle size and in vitro drug diffusion of the prepared microspheres. Microspheres were evaluated for particle size, entrapment efficiency, swelling property, in vitro mucoadhesion, in vitro drug diffusion, ex vivo drug permeation, histopathological examination and stability studies. The results of differential scanning calorimetry, X-ray diffraction and scanning electron microscopy revealed molecular dispersion of Valsartan into microspheres with spherical shape and smooth surface. Optimized formulation indicated good mucoadhesion with no severe sign of damage on nasal mucosa. Results of the non-invasive animal studies in dexamethasone-induced hypertensive rat model suggested the suitability of investigated drug delivery system for intranasal administration.

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 purpose of this study was to mask the intensely bitter taste of metoclopramide HCl and to formulate a rapid disintegrating tablet (RDT) of the taste-masked drug. Taste masking was done by complexing metoclopramide HCl with aminoalkyl methacrylate copolymer (Eudragit EPO) in different ratio by the extrusion-precipitation method. Drug-polymer complexes (DPCs) were tested for drug content, in vitro taste in simulated salivary fluid (SSF) of pH 6.8, taste evaluation in oral cavity and molecular property. The complex having drug-polymer ratio of 1 : 2 shows significant taste masking, confirmed by drug release in SSF and in-vivo taste evaluation; therefore, it was selected for further study. Taste evaluation of DPCs in human volunteers revealed considerable taste masking with the degree of bitterness below threshold value (0.5) within 10 s, whereas, metoclopramide HCl was rated intensely bitter with a score of +3 for 10 s. Tablets were evaluated for various parameters like tensile strength, wetting time, water absorption ratio, in-vitro disintegration time, and disintegration in oral cavity. The effect of diluents, lubricants and sweetening agent (Xylisorb) on the disintegration time was also evaluated. Tablets of batch F3 containing mannitol and microcrystalline cellulose in the ratio 1 : 1 and 8% w/w crosspovidone showed faster disintegration (within 20 s) than the marketed formulation (180 s). Good correlation between in vitro disintegration behavior and in the oral cavity was recognized. Tablets of batch F3 also revealed rapid drug release (t(90), 90 s) in SGF compared with marketed formulation (t(90), 600 s).

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.