Development and In Vitro Characterization of Chitosan-based Microspheres for Nasal Delivery of Promethazine

ABSTRACT

Conventional and composed promethazine-loaded microspheres were prepared by spray drying of chitosan solution systems and double water-in-oil-in-water (W/O/W) emulsion systems, respectively. Double emulsions were prepared in two different feed concentrations, with chitosan dissolved in both water phases, and ethylcellulose dissolved in oil phase. Swelling and bioadhesive properties of the microspheres depended on the chitosan content, type and the feed concentration of spray-dried system. Results obtained suggested that better ethylcellulose microcapsules with promethazine in the chitosan matrix were formed when less concentrated emulsion systems were spray-dried. Thus, in case of such a system, with ethylcellulose/chitosan weight ratio of 1:2, prolonged promethazine release was obtained.     

Biocompatibility study of theophylline/chitosan/β-cyclodextrin microspheres as pulmonary delivery carriers

To evaluate the biocompatibility of the theophylline/chitosan/β-cyclodextrin microspheres, which has a potential application in pulmonary delivery system. The detection of LDH and protein in BALF was examined acute cell toxicity, hemolysis test was carried out to estimate blood toxicity; Micronucleus Test was reckoned to identify genotoxicity, MTT assay was used to evaluate in vitro cytotoxicity, and muscle implantation investigated the tissue biocompatibility. The results demonstrated that the total contents of protein and LDH in BALF were not significantly different from that of normal group. The experiments showed that the cytotoxicity was depended on the concentration and had no cytoxicity at low concentration and no hemolysis activity. The micronucleus frequency of MS B was 0.99‰, which showed no genotoxic effects either. The results of implantation showed that the microspheres had no effect on hemoglobin and no toxicity in the liver and kidney. The inflammations of muscle tissue were not significantly different from that of operative suture, therefore, the MS B possess high good biocompatibility and can be applied in pulmonary sustained release systems.     

Ondansetron-loaded chitosan microspheres for nasal antiemetic drug delivery: an alternative approach to oral and parenteral routes

Background: The aim of this study was to develop chitosan microspheres for nasal delivery of ondansetron hydrochloride (OND). Method: Microspheres were prepared with spray-drying method using glutaraldehyde as the crosslinking agent. Microspheres were characterized in terms of morphology, particle size, zeta potential, production yield, drug content, encapsulation efficiency, and in vitro drug release. Results: All microspheres were spherical in shape with smooth surface and positively charged. Microspheres had also high encapsulation efficiency and the suitable particle size for nasal administration. In vitro studies indicated that all crosslinked microspheres had a significant burst effect, and sustained drug release pattern was observed until 24 hours following burst drug release. Nasal absorption of OND from crosslinked chitosan microspheres was evaluated in rats, and pharmacokinetic parameters of OND calculated from nasal microsphere administration were compared with those of both nasal and parenteral administration of aqueous solutions of OND. In vivo data also supported that OND-loaded microspheres were also able to attain a sustained plasma profile and significantly larger area under the curve values with respect to nasal aqueous solution of OND. Conclusion: Based on in vitro and in vivo data, it could be concluded that crosslinked chitosan microspheres are considered as a nasal delivery system of OND.     

Formulation and in vitro evaluation of bisphosphonate loaded microspheres for implantation in osteolysis

Chitosan and poly(lactide-co-glycolide) acid (PLGA) microspheres loaded with alendronate sodium (AS) were prepared for orthopedic as well as dental applications. In orthopedics the aim was to make the total joint prostheses stay in the body for a long time without causing bone tissue loss, while in dentistry it was aimed to treat the alveolar bone resorption caused by periodontitis and also to make the dental treatment using implants easier by reducing the bone loss in patients with osteoporosis. Solvent evaporation method was used to prepare AS loaded PLGA microspheres and emulsion polimerization method was used to prepare AS loaded chitosan microspheres. Particle size, loading efficacy, surface characteristics, and in vitro release characteristics were examined on prepared formulations. After the examination of the scanning electron microscopy photographs of microspheres, chitosan microspheres were observed to have spherical structure and smooth surface characteristics while PLGA microspheres were observed to have spherical porous surface structure. Loading efficacy was found to be 3.30% for chitosan microspheres and 7.70% for PLGA microspheres. It was observed that 85% of AS had been released at the end of the third day from chitosan microspheres whereas 58% was released at the end of the fifth day from PLGA microspheres. It was found that chitosan microspheres gave first order release while PLGA microspheres gave zero order release.     

Evaluation of PLGA microspheres as delivery system for antitumor agent-camptothecin

Camptothecin (CPT) and its analogues are a new class of anticancer agents that have been identified over the past several years. Camptothecin exists in two forms depending on the pH: An active lactone form at pH below 5 and an inactive carboxylate form at basic or physiological neutral pH. Poly(lactide-co-glycolide) (PLGA) microspheres have been considered good delivery vehicles for CPT because of acidic microenvironment formed through PLGA degradation. The objective of this study is to investigate antitumor activity of CPT after it is encapsulated in PLGA microspheres. In this study, PLGA microspheres containing various CPT loadings were prepared and characterized. Cytotoxicity of these microspheres to B16 melanoma cells was then evaluated, and uptake of microspheres by B16 cells was also studied. Analysis of drug stability revealed that CPT is released from the microspheres in its active lactone form over the entire release duration. It was also found that there was no interaction between CPT and PLGA matrix within microspheres through Differential Scanning Calorimetry (DSC) and Fourien Transform Infrared Spectroscopy (FT-IR) and hign performance liquid chromatography (HPLC) studies. Cytotoxicity assay showed that CPT encapsulated in PLGA microspheres still retained its antitumor potency. Uptake study revealed quick uptake of the microspheres by B16 cells, which was desirable. It was concluded that PLGA microspheres were suitable delivery vehicles to stabilize and deliver CPT for the treatment of cancer.     

Development and gamma-scintigraphy study of Hibiscus rosasinensis polysaccharide-based microspheres for nasal drug delivery

Objective: This work describes the application of natural plant polysaccharide as pharmaceutical mucoadhesive excipients in delivery systems to reduce the clearance rate through nasal cavity.

Methods: Novel natural polysaccharide (Hibiscus rosasinensis)-based mucoadhesive microspheres were prepared by using emulsion crosslinking method for the delivery of rizatriptan benzoate (RB) through nasal route. Mucoadhesive microspheres were characterized for different parameters and nasal clearance of technetium-99m (^99mTc)-radiolabeled microspheres was determined by using gamma-scintigraphy.

Results: Their Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD) studies showed that the drug was stable during preparation of microspheres. Aerodynamic diameter of microspheres was in the range 13.23?±?1.83–33.57?±?3.69?µm. Change in drug and polysaccharide ratio influenced the mucoadhesion, encapsulation efficiency and in-vitro release property. Scintigraphs taken at regular interval indicate that control solution was cleared rapidly from nasal cavity, whereas microspheres showed slower clearance (p?Conclusion: Natural polysaccharide-based microspheres achieved extended residence by minimizing effect of mucociliary clearance with opportunity of sustained delivery for longer duration.     

Formulation and in vitro characterization of long-acting PLGA injectable microspheres encapsulating a peptide analog of LHRH

The present study aimed to formulate triptorelin acetate(TA)into poly(D,L-lactic-co-glycolic)acid(PLGA)based injectable sustained-release microspheres(TA-PLGA-MS)by usingdouble emulsion solvent extraction/evaporation(DESE)technique and investigate the effects of various material attributes and process parameters on the quality attributes such as size,shape,surface morphology,encapsulation efficiency(EE)and in vitro release behavior of these microspheres.Variable compositions of the outer water phase,type of the organic solvents,volume ratios of inner water phase to oil phase,PLGA concentrations,and the powers for emulsification in the preparation of the microspheres showed an influence on their quality attributes.An optimal formulation(F-2)obtained from this univariate approach possess an excellent EE value of 63.5%±3.4%and an average volumetric particle size of 35.3±1.8μm.This formulation was further accomplished with different solidification rates assisted by variable incubation temperatures,which exhibited an impact on the shape/surface and inner morphology of the microspheres.The resultant microspheres also displayed different in vitro release patterns.The matrices processed with a high incubation temperature conferred the fastest and the most complete drug release profile over the period of 63 days.Thus,the solidification rate could be identified as one of the critical process parameters that affected the quality of the PLGA based injectable microspheres specifically designed for the prolonged delivery of TA.     

Preparation of alginate microspheres by water-in-oil emulsion method for drug delivery: Effect of Ca2+ post-cross-linking

Alginate microspheres were prepared by a water-in-oil emulsion solvent diffusion method. The alginate microspheres were post-cross-linked with Ca²⁺ ions. Influence of Ca²⁺ concentration on the characteristics and drug release behaviors of alginate microspheres was evaluated. Blue dextran was used as a water-soluble model drug. The non-cross-linked alginate microspheres were less than 100 μm in size and had a spherical shape. The cross-linked alginate microspheres were also spherical in shape with a rougher surface but their particle sizes were larger than 100 μm. The drug encapsulation efficiency of the non-cross-linked alginate microspheres was very high (82%). The drug encapsulation efficiency of alginate microspheres cross-linked with 5% and 10% Ca²⁺ concentrations were similar to the non-cross-linked microspheres. The in vitro drug releases of the cross-linked alginate microspheres showed prolong release profiles. The cumulative release of blue dextran decreased as the Ca²⁺ concentration increased. Thus, Ca²⁺-post-cross-linked alginate microspheres show possibility for use as controlled-release drug carriers.     

Formulation and characterization of intranasal mucoadhesive nanoparticulates and thermo-reversible gel of levodopa for brain delivery

Levodopa is the drug of choice in the treatment of Parkinson’s disease but it exhibits low oral bioavailability (30%) and very low brain uptake due to its extensive metabolism by aromatic amino acid decarboxylase in the peripheral circulation. Hence, levodopa is co-administered with carbidopa, a peripheral amino acid decarboxylase inhibitor. In an attempt to improve brain uptake and to avoid degradation of levodopa in peripheral circulation and the use of carbidopa in combination, nose to brain drug delivery of levodopa alone via the olfactory route and the trigeminal nerves has been investigated. Chitosan nanoparticles loaded with levodopa (CNL) were prepared and were incorporated in a thermo-reversible gel prepared using Pluronic PF127 (CNLPgel). The preparation of CNL and CNLPgel was optimized for formulation parameters such as chitosan:TPP ratio, drug load Pluronic concentration to obtain desired particle size of CNL, gelling temperature, gelling time and mucoadhesive strength of CNLPgel. Rheological studies indicated a change in the rheological behavior of plain pluronic gel from Newtonian system at 30?°C to pseudoplastic behavior at 35?°C on incorporation of CNL. In vitro release studies from CNL obeyed Higuchi kinetic model, whereas the drug release from CNLPgel followed the Hixson–Crowell model. In vivo studies indicated a maximum recovery of the drug in brain following intranasal administration of CNL suspension in saline closely followed by the drug dispersed in plain pluronic gel.     

Novel nano-cellulose excipient for generating non-Newtonian droplets for targeted nasal drug delivery

Purpose: Thickening polymers have been used as excipients in nasal formulations to avoid nasal run-off (nasal drip) post-administration. However, increasing the viscosity of the formulation can have a negative impact on the quality of the aerosols generated. Therefore, the study aims to investigate the use of a novel smart nano-cellulose excipient to generate suitable droplets for nasal drug delivery that simultaneously has only marginally increased viscosity while still reducing nasal drips.

Methods: Nasal sprays containing nano-cellulose at different concentrations were investigated for the additive’s potential as an excipient. The formulations were characterized for their rheological and aerosol properties. This was then compared to conventional nasal spray formulation containing the single-component hydroxyl-propyl methyl cellulose (HPMC) viscosity enhancing excipient.

Results: The HPMC-containing nasal formulations behave in a Newtonian manner while the nano-cellulose formulations have a yield stress and shear-thinning properties. At higher excipient concentrations and shear rates, the nano-cellulose solutions have significantly lower viscosities compared to the HPMC solution, resulting in improved droplet formation when actuated through conventional nasal spray.

Conclusions: Nano-cellulose materials could potentially be used as a suitable excipient for nasal drug delivery, producing consistent aerosol droplet size, and enhanced residence time within the nasal cavity with reduced run-offs compared to conventional polymer thickeners.     

Development and in vitro characterization of self-emulsifying drug delivery system (SEDDS) for oral opioid peptide delivery

Aim: In this study, self-emulsifying drug delivery system (SEDDS) for oral delivery of opioid peptide dalargin were developed and characterized in vitro.

Methods: Dalargin lipophilicity was increased by O-esterification of tyrosine OH group, hydrophobic ion pairing, or a combination thereof. Distribution coefficients (log?D) of lipidized dalargin derivatives were determined. Then, dalargin was incorporated in chosen SEDDS, namely SEDDS-1, composed of 50% Capmul 907, 40% Cremophor EL, and 10% propylene glycol and comparatively more lipophilic SEDDS-2 composed of 30% Captex 8000, 30% Capmul MCM, 30% Cremophor EL, and 10% propylene glycol. Additionally, SEDDS were characterized regarding droplet size, polydispersity index (PDI), cloudy point, physical stability and stability against pancreatic lipase. Furthermore, mucus permeating properties of SEDDS and their ability to protect the incorporated dalargin against proteolysis by trypsin, α-chymotrypsin, elastase, simulated gastric fluid (SGF), and simulated intestinal fluid (SIF) were evaluated.

Results: The highest dalargin drug payload of 4.57% in SEDDS-2 was achieved when dalargin palmitate (pDAL) was ion paired with sodium dodecyl sulfate (SDS) in molar ratio 1:1. Moreover, SEDDS-1 and SEDDS-2 had a narrow droplet size distribution with average droplet sizes of 42.1 and 33.1?nm with PDI of 0.042 and 0.034, respectively. Lipolysis study showed that within 30?min 78.5% of SEDDS-1 and 92.1% of SEDDS-2 were digested. In addition, both SEDDS exhibited mucus permeating properties as well as a protective effect against enzymatic degradation by trypsin, α-chymotrypsin, elastase, SGF and SIF.

Conclusion: The results of this study suggest that the developed SEDDS could be considered for oral opioid peptide delivery.     

Development and in vitro evaluation of a nanoemulsion for transcutaneous delivery

Objective: The purpose of this study is to develop a nanoemulsion formulation for its use as a transcutaneous vaccine delivery system.

Materials and methods: With bovine albumin-fluorescein isothiocyanate conjugate (FITC-BSA) as a vaccine model, formulations were selected with the construction of pseudo-ternary phase diagrams and a short-term stability study. The size of the emulsion droplets was furthered optimized with high-pressure homogenization. The optimized formulation was evaluated for its skin permeation efficiency. In vitro skin permeation studies were conducted with shaved BALB/c mice skin samples with a Franz diffusion cell system. Different drug concentrations were compared, and the effect of the nanoemulsion excipients on the permeation of the FITC-BSA was also studied.

Results: The optimum homogenization regime was determined to be five passes at 20?000?psi, with no evidence of protein degradation during processing. With these conditions, the particle diameter was 85.2?nm?±?15.5?nm with a polydispersity index of 0.186?±?0.026 and viscosity of 14.6 cP?±?1.2 cP. The optimized formulation proved stable for 1 year at 4?°C. In vitro skin diffusion studies show that the optimized formulation improves the permeation of FITC-BSA through skin with an enhancement ratio of 4.2 compared to a neat control solution. Finally, a comparison of the skin permeation of the nanoemulsion versus only the surfactant excipients resulted in a steady state flux of 23.44?μg/cm²/h for the nanoemulsion as opposed to 6.10?μg/cm²/h for the emulsifiers.

Conclusion: A novel nanoemulsion with optimized physical characteristics and superior skin permeation compared to control solution was manufactured. The formulation proposed in this study has the flexibility for the incorporation of a variety of active ingredients and warrants further development as a transcutaneous vaccine delivery vehicle.     

Development of a Soluplus budesonide freeze-dried powder for nasal drug delivery

Objective: The aim of this work was to develop an amorphous solid dispersions/solutions (ASD) of a poorly soluble drug, budesonide (BUD) with a novel polymer Soluplus^® (BASF, Germany) using a freeze-drying technique, in order to improve dissolution and absorption through the nasal route.

Significance: The small volume of fluid present in the nasal cavity limits the absorption of a poorly soluble drug. Budesonide is a corticosteroid, practically insoluble and normally administered as a suspension-based nasal spray.

Methods: The formulation was prepared through freeze-drying of polymer-drug solution. The formulation was assessed for its physicochemical (specific surface area, calorimetric analysis and X-ray powder diffraction), release properties and aerodynamic properties as well as transport in vitro using RPMI 2650 nasal cells, in order to elucidate the efficacy of the Soluplus–BUD formulation.

Results: The freeze-dried Soluplus–BUD formulation (LYO) showed a porous structure with a specific surface area of 1.4334?±?0.0178 m²/g. The calorimetric analysis confirmed an interaction between BUD and Soluplus and X-ray powder diffraction the amorphous status of the drug. The freeze-dried formulation (LYO) showed faster release compared to both water-based suspension and dry powder commercial products. Furthermore, a LYO formulation, bulked with calcium carbonate (LYO-Ca), showed suitable aerodynamic characteristics for nasal drug delivery. The permeation across RPMI 2650 nasal cell model was higher compared to a commercial water-based BUD suspension.

Conclusions: Soluplus has been shown to be a promising polymer for the formulation of BUD amorphous solid suspension/solution. This opens up opportunities to develop new formulations of poorly soluble drug for nasal delivery.     

Preparation and in vitro characterization of pluronic-attached polyamidoamine dendrimers for drug delivery

Context: Polyamidoamine (PAMAM) dendrimers have attracted lots of interest as drug carriers. And little study about whether pluronic-attached PAMAM dendrimers could be potential drug delivery systems has been carried on.

Objective: Pluronic F127 (PF127) attached PAMAM dendrimers were designed as novel drug carriers.

Methods: Two conjugation ratios of PF127-attached PAMAM dendrimers were synthesized. ¹H nuclear magnetic resonance (¹H-NMR), Fourier transform infrared spectrum (FTIR), element analysis and ninhydrin assay were used to characterize the conjugates. Size, zeta potential and critical micelle concentrations (CMC) were also detected. And DOX was incorporated into the hydrophobic interior of the conjugates. Studies on their drug loading and drug release were carried on. Furthermore, hemolysis and cytotoxicity assay were used to evaluate the toxicity of the conjugates.

Results and discussion: PF127 was successfully conjugated to the fifth generation PAMAM dendrimer at two molar ratios of 19% and 57% (PF127 to surface amine per PAMAM dendrimer molecular). The conjugates showed an increased size and a reduced zeta potential. And higher CMC values were obtained than pure PF127. Compared with unconjugated PAMAM dendrimer, PF127 conjugation significantly reduced the hemolytic toxicity and cytotoxicity of PAMAM dendrimer in vitro. The encapsulation results showed that the ability to encapsulate DOX by the conjugate of 19% conjugation ratio was better than that of 57% conjugation ratio. And the maximum is ～12.87 DOX molecules per conjugate molecule. Moreover, the complexes showed a sustained release behavior compared to pure DOX.

Conclusion: Findings from the in vitro study show that the PF127-attached PAMAM dendrimers may be potential carriers for drug delivery.     

Insulin nanoparticles for transdermal delivery: preparation and physicochemical characterization and in vitro evaluation

Aim: This work is aimed to study the feasibility of insulin nanoparticles for transdermal drug delivery (TDD) using supercritical antisolvent (SAS) micronization process. Methods: The influences of various experimental factors on the mean particle size (MPS) of insulin nanoparticles were investigated. Moreover, the insulin nanoparticles obtained were characterized by scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), and thermogravimetric (TG) analyses. Results: Under optimum conditions, uniform spherical insulin nanoparticles with a MPS of 68.2?±?10.8 nm were obtained. The Physicochemical characterization results showed that SAS process has not induced degradation of insulin. Evaluation in vitro showed that insulin nanoparticles were accorded with the Fick's first diffusion law and had a high permeation rate. Conclusion: These results suggest that insulin nanoparticles can have a great potential in TDD systems of diabetes chemotherapy.     

Preparation and characterization of spray-dried submicron particles for pharmaceutical application

The versatile use of submicron-sized particles (0.1–1?μm) requires new manufacturing methods. One possibility for the preparation of submicron-sized particles is spray drying. However, the generation of small droplets at a high production rate and the precipitation of submicron particles are quite challenging. In order to produce a sufficient amount of fine and uniform droplets, a two-fluid nozzle with internal mixing was combined with a cyclone droplet separator. The precipitation of particles was realized with an electrostatic precipitator. Considering the difficulty of electrostatic precipitation concerning explosion risks and to make it capable using organic solvents, the spray dryer was integrated in a pressure resistant vessel. Based on previous experiments, the now presented design is compact and the electrostatic precipitator is shortened. In addition, enhanced drying conditions ensured a controlled and reproducible preparation of submicron-sized particles. Thus, high separation efficiencies were shown. Spray-drying experiments were conducted with the model substance mannitol. With the cyclone droplet separator, a fine and uniform spray with a droplet size smaller 2?μm was produced. This robust atomizing technique is capable for high concentrations. For a 10?wt% mannitol solution, particles in the submicron range d_50,3?=?0.7?μm were produced.     

Cholesterol derivative-based liposomes for gemcitabine delivery: preparation,in vitro,and in vivo characterization

As an anti-tumor drug, gemcitabine (Gem) is commonly used for the treatment of non-small cell lung cancer and pancreatic cancer. However, there are several clinical drawbacks to using Gem, including its extremely short plasma half-life and side effects. To prolong its half-life and reduce its side effects, we synthesized a derivative of Gem using cholesterol (Chol). This derivative, called gemcitabine-cholesterol (Gem-Chol), was entrapped into liposomes by a thin-film dispersion method. The particle size of the Gem-Chol liposomes was 112.57?±?1.25?nm, the encapsulation efficiency was above 99%, and the drug loading efficiency was about 50%. In vitro studies revealed that the Gem-Chol liposomes showed delayed drug release and long-term stability at 4?°C for up to 2 months. In vivo studies also showed the superiority of the Gem-Chol liposomes, and compared with free Gem, the Gem-Chol liposomes had longer circulation time. Moreover, an anti-tumor study in H₂₂ and S180 tumor models showed that liposomal entrapment of Gem-Chol improved the anti-tumor effect of Gem. This study reports a potential formulation of Gem for clinical application.     

Development and in vitro evaluation of surface modified poly(lactide-co-glycolide) nanoparticles with chitosan-4-thiobutylamidine

The objective of this study was to develop a nanoparticulate drug delivery system based on the surface modification of poly(lactide-co-glycolide) (PLGA) nanoparticles with a thiolated chitosan. PLGA nanoparticles were prepared by the emulsification-solvent evaporation method. Immobilization of chitosan to the surface of PLGA nanoparticles via amide bonds was mediated by a carbodiimide. Thiol groups were covalently bound to the chitosan surface of particles by reaction with 2-iminothiolane. Obtained nanoparticles were characterized in vitro regarding size, zeta potential, thiol group content, stability at different pH values, mucoadhesion, and drug release. Results demonstrated that the surface modification of PLGA nanoparticles with thiolated chitosan (chitosan-TBA) leads to nanoparticles of a mean diameter of 889.5 ± 72 nm and positive zeta potential of + 24.74 mV. The modified nanoparticles contained 7.32 ± 0.24 μmol thiol groups per gram nanoparticles. The size of nanoparticles was strongly influenced by the pH of the surrounding medium, being 925.0 ± 76.3 nm at pH 2 and 577.8 ± 66.7 nm at pH 7.4. Thiolated nanoparticles showed a 3.3-fold prolonged residence time on the mucosa and an unchanged release profile in comparison to unmodified PLGA nanoparticles. These data suggest that surface modified chitosan-TBA conjugate PLGA nanoparticles have the potential to be used as mucoadhesive drug delivery system.     

Preparation and in vitro evaluation of chitosan microspheres containing prednisolone: comparison of simple and conjugate microspheres

The purpose of the present study was to obtain a novel microparticulate formulation of prednisolone, which was adequate for the treatment of inflammatory bowel disease (IBD). The formulations prepared were evaluated in vitro. Two types of chitosan microspheres containing prednisolone, named Ch-Pred and Ch-SP-MS, were prepared by an emulsification-solvent evaporation method using a chitosan-prednisolone mixture and a chitosan-succinyl-prednisolone conjugate (Ch-SP), respectively. Ch-Pred and Ch-SP-MS were obtained in almost spherical shape. Ch-Pred showed a relatively high drug content of 13.2% (w/w), but the particle size was distributed from 10 to 45 µm, and a large initial burst release of approximately 60% was observed. On the other hand, although Ch-SP-MS exhibited a fairly low drug content of 3.5% (w/w), their particle size ranged from several hundred nanometers to 20 µm, with the mean diameter of 5 µm, and a gradual drug release profile was achieved. These characteristics on particle size and in vitro release suggested that Ch-SP-MS should have good potential as a microparticulate system for the treatment of IBD.     

Fast-drying multi-laminate bioadhesive films for transdermal and topical drug delivery

No bioadhesive patch-based system is currently marketed. This is despite an extensive number of literature reports on such systems detailing their advantages over conventional pressure sensitive adhesive-based patches in wet environments and describing successful delivery of a diverse array of drug substances. This lack of proprietary bioadhesive patches is largely due to the fact that such systems are exclusively water-based, meaning drying is difficult. In this paper we describe, for the first time, a novel multiple lamination method for production of bioadhesive patches. In contrast to patches produced using a conventional casting approach, which took 48 hours to dry, bioadhesive films prepared using the novel multiple lamination method were dried in 15?min and were folded into formed patches in a further 10?min. Patches prepared by both methods had comparable physicochemical properties. The multiple lamination method allowed supersaturation of 5-aminolevulinic acid to be achieved in formed patch matrices. However, drug release studies were unable to show an advantage for supersaturation with this particular drug, due to its water high solubility. The multiple lamination method allowed greater than 90% of incorporated nicotine to remain within formed patches, in contrast to the 48% achieved for patches prepared using a conventional casting approach. The procedure described here could readily be adapted for automation by industry. Due to the reduced time, energy and ensuing finance now required, this could lead to bioadhesive patch-based drug delivery systems becoming commercially viable. This would, in turn, mean that pathological conditions occurring in wet or moist areas of the body could now be routinely treated by prolonged site-specific drug delivery, as mediated by a commercially produced bioadhesive patch.