Formulation, characterisation and stabilisation of buccal films for paediatric drug delivery of omeprazole.

This study aimed to develop films for potential delivery of omeprazole (OME) via the buccal mucosa of paediatric patients. Films were prepared using hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), carrageenan (CA) and metolose (MET) with polyethylene glycol (PEG 400) as plasticiser, OME (model drug) and L-arg (stabiliser). Gels (1% w/w) were prepared at 40°C using water and ethanol with PEG 400 (0-1% w/w) and dried in an oven (40°C). Optimised formulations containing OME and L-arg (1:1, 1:2 and 1:3) were prepared to investigate the stabilisation of the drug. Tensile properties (Texture analysis, TA), physical form (differential scanning calorimetry, DSC; X-ray diffraction, XRD; thermogravimetric analysis, TGA) and surface topography (scanning electron microscopy, SEM) were investigated. Based on the TA results, SA and MET films were chosen for OME loading and stabilisation studies as they showed a good balance between flexibility and toughness. Plasticised MET films were uniform and smooth whilst unplasticised films demonstrated rough lumpy surfaces. SA films prepared from aqueous gels showed some lumps on the surface, whereas SA films prepared from ethanolic gels were smooth and uniform. Drug-loaded gels showed that OME was unstable and therefore required addition of L-arg. The DSC and XRD suggested molecular dispersion of drug within the polymeric matrix. Plasticised (0.5% w/w PEG 400) MET films prepared from ethanolic (20% v/v) gels and containing OME: L-arg 1:2 showed the most ideal characteristics (transparency, ease of peeling and flexibility) and was selected for further investigation.

Preparation and characterization of laminated thiolated chitosan-based freeze-dried wafers for potential buccal delivery of macromolecules.

This study involves the development and functional characterization of a thiolated chitosan (CS) system for potential buccal delivery of proteins. Thiolated CS was synthesized by conjugating pure CS with thioglycolic acid and dialyzed to remove excess acid. Amount of thiol groups immobilized on CS was determined using L-cysteine calibration curve. The weight average molecular weights of CS and thiolated CS were monitored using gel permeation chromatography. Laminated wafers were obtained by pouring gels (containing bovine serum albumin; BSA, different amounts of glutathione as enzyme inhibitor and mucin to mimic salivary conditions) of the thiolated CS into moulds previously lined with impervious ethylcellulose (EC) films and freeze-dried. The resulting formulations were analyzed using attenuated total reflectance Fourier transform infrared (FTIR) spectroscopy, circular dichroism (CD) and scanning electron microscopy (SEM). The formulations were further characterized for functional buccal mucosa performance using hydration, swelling, mucoadhesion and in vitro drug dissolution studies. FTIR showed successful thiolation of CS's amine functionality, CD confirmed that BSA conformation remained unchanged throughout the gel formulation and freeze-drying process, whilst SEM showed a porous microstructure of the wafers and a uniform EC film laminate with no visible pores or cracks. The functional characterization studies showed that glutathione had significant effects on hydration, mucoadhesion and subsequently drug dissolution and release characteristics, whilst mucin affected the mucoadhesive properties of the wafers. It was concluded that BSA-loaded wafers containing 10% w/w glutathione as enzyme inhibitor was the formulation choice for potential buccal delivery and should be selected for further investigations.

Development and physico-mechanical characterization of carrageenan and poloxamer-based lyophilized matrix as a potential buccal drug delivery system.

CONTEXT AND OBJECTIVES: The buccal mucosa presents a unique surface for non-invasive drug delivery and also avoids first-pass metabolism. The objective of this study was the formulation development of polymeric mucoadhesive lyophilized wafers as a matrix for potential buccal drug delivery. MATERIALS AND METHODS: Differential scanning calorimetry (DSC) was used to develop an optimum freeze-cycle, incorporating an annealing step. The wafers were prepared by lyophilization of gels containing three polymers, κ-carrageenan (CAR 911), poloxamer (P407) and polyethylene glycol 600 (PEG 600). The formulations were characterized using texture analysis (for mechanical and mucoadhesion properties), hydration studies, thermogravimetric analysis (TGA), DSC, X-ray powder diffraction (XRPD) and scanning electron microscopy (SEM). RESULTS AND DISCUSSION: DSC showed the eutectic temperature (12.8 °C) of the system where the liquid solution and pure solids both existed at a fixed pressure which helped determine the freeze-annealing cycle at 55 °C for 7 h. Mechanical resistance to compression, hydration and mucoadhesion studies showed that optimized wafers were obtained from aqueous gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600. TGA showed residual water of approximately 1% and SEM showed a porous polymeric network that made ease of hydration possible. CONCLUSIONS: Lyophilized wafers by freeze-drying gels containing 2% w/w CAR 911, 4% w/w P407 and 4.4% w/w PEG 600 with optimum physico-mechanical properties has been achieved.

A review on the taste masking of bitter APIs: hot-melt extrusion (HME) evaluation.

The majority of active pharmaceutical ingredients (APIs) found in oral dosage forms have a bitter taste. Masking the unpleasant taste of bitter, APIs is a major challenge in the development of such oral dosage forms. Taste assessment is an important quality-control parameter for evaluating taste-masked formulations of any new molecular entity. Hot-melt extrusion (HME) techniques, have very recently, been accepted from an industrial compliance viewpoint in relation to both manufacturing operations and development of pharmaceuticals. HME achieves taste masking of bitter APIs via various mechanisms such as the formation of solid dispersions and inter-molecular interactions and this has led to its wide-spread use in pharmaceutical formulation research. In this article, the uses of various taste evaluation methods and HME as continuous processing techniques for taste masking of bitter APIs used for the oral delivery of drugs are reviewed.

Novel films for drug delivery via the buccal mucosa using model soluble and insoluble drugs.

Bioadhesive buccal films are innovative dosage forms with the ability to adhere to the mucosal surface and subsequently hydrate to release and deliver drugs across the buccal membrane. This study aims to formulate and characterize stable carrageenan (CAR) based buccal films with desirable drug loading capacity. The films were prepared using CAR, poloxamer (POL) 407, various grades of PEG (plasticizer) and loaded with paracetamol (PM) and indomethacin (IND) as model soluble and insoluble drugs, respectively. The films were characterized by texture analysis, thermogravimetric analysis (TGA), DSC, scanning electron microscopy, X-ray powder diffraction (XRPD), and in vitro drug release studies. Optimized films were obtained from aqueous gels comprising 2.5% w/w κ-CAR 911, 4% w/w POL 407 and 6% w/w (PM) and 6.5% w/w (IND) of PEG 600 with maximum drug loading of 1.6% w/w and 0.8 % w/w for PM and IND, respectively. TGA showed residual water content of approximately 5% of films dry weight. DSC revealed a T(g) at 22.25 and 30.77°C for PM and IND, respectively, implying the presence of amorphous forms of both drugs which was confirmed by XRPD. Drug dissolution profiles in simulated saliva showed cumulative percent release of up to 45 and 57% of PM and IND, respectively, within 40 min of contact with dissolution medium simulating saliva.

Comparison of the in vitro release characteristics of mucosal freeze-dried wafers and solvent-cast films containing an insoluble drug.

Drug release characteristics of freeze-dried wafers and solvent-cast films prepared from sodium carboxymethylcellulose have been investigated and compared. In vitro drug dissolution studies were performed using an exchange cell and drug release was measured by UV spectroscopy at 272 nm using distilled water. The dissolution profiles of hydrochlorothiazide from the wafers and films were compared by determining the rates of drug release, estimated from the % release versus time profiles and calculating their difference (f(1)) and similarity (f(2)) factors. The effects of drug loading, polymer content and amount of glycerol (GLY) (films) on the drug release characteristics of both formulations were investigated. Both the wafers and films showed sustained type release profiles that were best explained by the Korsmeyer-Peppas equation. Changes in the concentration of drug and GLY (films) did not significantly alter the release profiles whilst increasing polymer content significantly decreased the rate of drug release from both formulations. The rate of release was faster from the wafers than the corresponding films which could be attributed to differences in the physical microstructure. The results show the potential of employing both formulations in various mucosal drug delivery applications.

Development of 3D printed drug-eluting contact lenses.

OBJECTIVES: The aim of the work was to introduce 3D printing technology for the design and fabrication of drug-eluting contact lenses (DECL) for the treatment of glaucoma. The development of 3D printed lenses can effectively overcome drawbacks of existing approaches by using biocompatible medical grade polymers that provide sustained drug release of timolol maleate for extended periods. METHODS: Hot melt extrusion was coupled with fusion deposition modelling (FDM) to produce printable filaments of ethylene-vinyl acetate copolymer-polylactic acid blends at various ratios loaded with timolol maleate. Physicochemical and mechanical characterisation of the printed filaments was used to optimise the printing of the contact lenses. KEY FINDINGS: 3D printed lenses with an aperture (opening) and specified dimensions could be printed using FDM technology. The lenses presented a smooth surface with good printing resolution while providing sustained release of timolol maleate over 3 days. The findings of this study can be used for the development of personalised DECL in the future.

Wound dressings as growth factor delivery platforms for chronic wound healing.

Introduction: Years of tissue engineering research have clearly demonstrated the potential of integrating growth factors (GFs) into scaffolds for tissue regeneration, a concept that has recently been applied to wound dressings. The old concept of wound dressings that only take a passive role in wound healing has now been overtaken, and advanced dressings which can take an active part in wound healing, are of current research interest.Areas covered: In this review we will focus on the recent strategies for the delivery of GFs to wound sites with an emphasis on the different approaches used to achieve fine tuning of spatial and temporal concentrations to achieve therapeutic efficacy.Expert opinion: The use of GFs to accelerate wound healing and reduce scar formation is now considered a feasible therapeutic approach in patients with a high risk of infections and complications. The integration of micro - and nanotechnologies into wound dressings could be the key to overcome the inherent instability of GFs and offer adequate control over the release rate. Many investigations have led to encouraging outcomes in various in vitro and in vivo wound models, and it is expected that some of these technologies will satisfy clinical needs and will enter commercialization.

In vitro, ex vivo and in vivo evaluation of taste masked low dose acetylsalicylic acid loaded composite wafers as platforms for buccal administration in geriatric patients with dysphagia.

This study reports the development and characterization of taste masked, freeze-dried composite wafers for potential oral and buccal delivery of low dose aspirin (acetylsalicylic acid) to prevent thrombosis in elderly patients with dysphagia. The wafers were formulated by combining metolose (MET) with carrageenan (CAR), MET with chitosan (CS) at low molecular weight or CAR with CS using 45% v/v ethanol as solvent for complete solubilization of acetylsalicylic acid. Each wafer contained 75 mg of acetylsalicylic acid and sweetener (sucralose, stevia or aspartame) with a drug: sweetener ratio of 1:1 w/w. The formulations were characterized for physical properties using texture analyzer (hardness and mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), Fourier transform infrared (FTIR) spectroscopy, swelling capacity, and in vitro drug dissolution. Further, permeation studies with three different models (Permeapad™ artificial barrier, EpiOral™ and porcine buccal mucosa) using HPLC, cell viability using MTT assay and in vivo taste masking evaluation using human volunteers were undertaken. The sweeteners increased the hardness and adhesion of the wafers, XRD showed the crystalline nature of the samples which was attributed to acetylsalicylic acid, SEM confirmed a compacted polymer matrix due to recrystallized acetylsalicylic acid and sweeteners dispersed over the surface. Drug dissolution studies showed that acetylsalicylic acid was rapidly released in the first 20 min and then continuously over 1 h. EpiOral™ had a higher cumulative permeation than porcine buccal tissue and Permeapad™ artificial barrier, while MTT assay using Vero cells (ATCC® CCL-81) showed that the acetylsalicylic acid loaded formulations were non-toxic. In vivo taste masking study showed the ability of sucralose and aspartame to mask the bitter taste of acetylsalicylic acid and confirm that acetylsalicylic acid loaded MET:CAR, CAR:CS and MET:CS composite wafers containing sucralose or aspartame have potential for buccal delivery of acetylsalicylic acid in geriatric patients with dysphagia.

Surface Modification of Mobile Composition of Matter (MCM)-41 Type Silica Nanoparticles for Potential Oral Mucosa Vaccine Delivery.

Development of mobile composition of matter (MCM)-41 silica nanoparticles faces challenges, e.g. surface charge properties, antigen loading efficiency, protecting from enzymes and harsh GIT environment and effective release at target mucosal site. We report the production and characterization of polymer and amine modified MCM-41 type silica nanoparticles for oral antigen delivery using ovalbumin (OVA) as model antigen. Nanoparticles were characterized by dynamic light scattering (DLS), differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM), Brunauer-Emmett-Teller (BET) analysis, circular dichroism (CD), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), mucin binding, stability in simulated gastric fluid (SGF) and simulated intestinal fluid (SIF) and in vitro OVA release in SGF and SIF. Unmodified nanoparticles size of 146 nm increased to 175-321 nm after modification while modified particles remained intact for more than 3 h in SGF and 96 h in SIF (DLS and SEM). Mucin binding proved polyethylene glycol (PEG) and chitosan modified nanoparticles as potential candidates for oral mucosa delivery. Both showed highest OVA encapsulation at 67% and 73%, and sustained OVA release in SIF (96 h) at 65% and 64% respectively. BET results showed that nanopores were not blocked during surface modification. CD and SDS-PAGE showed that OVA conformational structure did not change after release from the nanoparticles.

Development and mechanical characterization of solvent-cast polymeric films as potential drug delivery systems to mucosal surfaces.

Solvent-cast films from three polymers, carboxymethylcellulose (CMC), sodium alginate (SA), and xanthan gum, were prepared by drying the polymeric gels in air. Three methods, (a) passive hydration, (b) vortex hydration with heating, and (c) cold hydration, were investigated to determine the most effective means of preparing gels for each of the three polymers. Different drying conditions [relative humidity - RH (6-52%) and temperature (3-45 degrees C)] were investigated to determine the effect of drying rate on the films prepared by drying the polymeric gels. The tensile properties of the CMC films were determined by stretching dumbbell-shaped films to breaking point, using a Texture Analyser. Glycerol was used as a plasticizer, and its effects on the drying rate, physical appearance, and tensile properties of the resulting films were investigated. Vortex hydration with heating was the method of choice for preparing gels of SA and CMC, and cold hydration for xanthan gels. Drying rates increased with low glycerol content, high temperature, and low relative humidity. The residual water content of the films increased with increasing glycerol content and high relative humidity and decreased at higher temperatures. Generally, temperature affected the drying rate to a greater extent than relative humidity. Glycerol significantly affected the toughness (increased) and rigidity (decreased) of CMC films. CMC films prepared at 45 degrees C and 6% RH produced suitable films at the fastest rate while films containing equal quantities of glycerol and CMC possessed an ideal balance between flexibility and rigidity.

Comparison and process optimization of PLGA, chitosan and silica nanoparticles for potential oral vaccine delivery.

Aim: The study compared performance of nanoparticles prepared from synthetic organic, natural organic and inorganic materials as vaccine delivery platforms. Materials & methods: Various formulation (concentration, polymer/silica:surfactant ratio, solvent) and process parameters (homogenization speed and time, ultrasonication) affecting functional performance characteristics of poly(lactic-co-glycolic acid) (PLGA), chitosan and silica-based nanoparticles containing bovine serum albumin were investigated. Nanoparticles were characterized using dynamic light scattering, x-ray diffraction, scanning/transmission electron microscopy, Fourier transform infrared spectroscopy and in vitro protein release. Results: Critical formulation parameters were surfactant concentration (PLGA, silica) and polymer concentration (chitosan). Optimized nanoparticles were spherical in shape with narrow size distribution and size ranges of 100-300 nm (blank) and 150-400 nm (protein loaded). Protein encapsulation efficiency was 26-75% and released within 48 h in a sustained manner. Conclusion: Critical formulation and process parameters affected size of PLGA, chitosan and silica nanoparticles and protein encapsulation, while silica produced the smallest and most stable nanoparticles.

Comparison of in vitro antibacterial activity of streptomycin-diclofenac loaded composite biomaterial dressings with commercial silver based antimicrobial wound dressings.

Infected chronic wounds heal slowly, exhibiting prolonged inflammation, biofilm formation, bacterial resistance, high exudate and ineffectiveness of systemic antimicrobials. Composite dressings (films and wafers) comprising polyox/carrageenan (POL-CAR) and polyox/sodium alginate (POL-SA), loaded with diclofenac (DLF) and streptomycin (STP) were formulated and tested for antibacterial activity against 2 × 105 CFU/mL of Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus representing infected chronic wounds and compared with marketed silver dressings. Minimum inhibitory concentration (MIC) showed higher values for DLF than STP due to non-conventional antibacterial activity of DLF. The DLF and STP loaded dressings were highly effective against E. coli, P. aeruginosa and S. aureus. POL-SA dressings were more effective against the three types of bacteria compared to POL-CAR formulations, while the DLF and STP loaded dressings showed greater antibacterial activity than the silver-based dressings. The films, showed greater antibacterial efficacy than both wafers and silver dressings. STP and DLF can act synergistically not only to kill the bacteria but also prevent their resistance and biofilm formation compared to silver dressings, while reducing chronic inflammation associated with infection.

Development and evaluation of performance characteristics of timolol-loaded composite ocular films as potential delivery platforms for treatment of glaucoma.

Thin and erodible polymeric films were developed as potential ocular drug delivery systems to increase drug retention on the eye with the aim of improving bioavailability and achieving controlled drug release. Two biocompatible film forming polymers, hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC), which are currently used as thickening agents in eye drops were employed. Two different films were prepared (i) as single polymer and (ii) as composite formulations by solvent casting method, incorporating glycerol (GLY) as plasticizer and timolol maleate (TM) as model glaucoma drug. After preliminary optimization of transparency and ease of handling, the formulations were further characterized for their physicochemical properties. No indication of significant drug-polymer or polymer-polymer (in composite films) interaction was observed from FTIR results while evaluation by IR mapping revealed uniform distribution of drug throughout the films. Amorphization of TM in the film matrix was confirmed by both DSC and XRD. Swelling studies illustrated remarkable swelling capacity of HA in comparison with HPMC which directly affected the drug release profiles, making HA a suitable polymer for controlled ocular drug delivery. Tensile and mucoadhesion properties confirmed higher elasticity and adhesiveness of HA while HPMC produced stronger films. The effect of sterilization by UV radiation on mechanical properties was also evaluated and showed no significant difference between the sterilized and non-sterilized films. The SEM results confirmed smoothness and homogeneity of film surfaces for all the formulations studied. The in vitro drug dissolution studies showed more extended release profiles of formulations containing HA. Cytotoxicity study (cell viability) using MTT assay on HeLa cells, confirmed that the single polymer and composite films are generally safe for ocular administration. The present work shows excellent film forming ability of HA and HPMC which can be used as single polymer or combined in composite formulations as potential topical ocular drug delivery platform to enhance drug retention on the ocular surface and therefore potential improved bioavailability.

Glassy state molecular mobility and its relationship to the physico-mechanical properties of plasticized hydroxypropyl methylcellulose (HPMC) films.

Changes in tensile properties and the glass transition temperature (Tg) of plasticized polymer films are typically attributed to molecular mobility, often with no empirical data to support such an assertion. Herein solvent cast HPMC films containing varying amounts of PEG, as the plasticizer, were used to assess the dependence of tensile properties and the Tg on glassy state molecular mobility. Molecular mobility (molecular relaxation time and temperature) parameters were determined by Thermally Stimulated Current Spectroscopy (TSC). The tensile properties and Tg of the HPMC films were determined by texture analysis and DSC, respectively. Molecular mobilities detected by TSC were cooperative and occurred at temperatures (Tg') well below (113 to 127 °C) the bulk Tg. The relaxation times (τ) were 71 ±â€¯1, 46 ±â€¯1, 42 ±â€¯1, 36 ±â€¯1 and 29 ±â€¯1 s for HPMC films containing 0, 6, 8, 11 and 17% (w/w) PEG, respectively. The Tg and glassy state molecular mobility were found to be intimately linked and demonstrated a linear dependence. While tensile strength was found to be linearly related to molecular relaxation time, tensile elongation and elastic modulus exhibited a non-linear dependence on molecular mobility. The data presented in this work demonstrates the complex nature of the relationship between plasticizer content, molecular mobility, Tg and tensile properties for plasticized polymeric films. It highlights the fact that the dependence of the bulk physico-mechanical properties on glassy state molecular mobility, differ greatly. Therefore, empirical characterization of molecular mobility is important to fully understand and predict the thermo-mechanical behavior of plasticized polymer films. This work demonstrates the unique capability of TSC to provide key information relating to molecular mobility and its influence on the bulk properties of materials. Data generated using TSC could prove useful for stability and performance ranking, in addition to the ability to predict materials behavior using data generated at or below typical storage conditions in the pharmaceutical, food, and polymer industries.

Oral thin films as a remedy for noncompliance in pediatric and geriatric patients.

Pediatric and geriatric patients experience swallowing difficulties for traditional oral dosage forms, such as tablets. Further, microbial contamination, chemical stability, unpleasant taste and swallowing large volumes of fluids have led to low therapeutic efficacy and patient noncompliance. The emergence of oral thin films has resulted in dramatic improvements in compliance and drug therapy outcomes in pediatric and geriatric patients. Oral thin films do not require water for administration, are readily hydrated upon contact with saliva, adhere to the mucosa and disintegrate ideally under 1 min. This article provides an overview of oral thin films, modern trends in their formulation and characterization, available commercial products, information to fill knowledge gaps and future potential and economic prospects of oral thin film technology, with emphasis on their use in the pediatric and geriatric patient groups.

Development and functional characterization of composite freeze dried wafers for potential delivery of low dose aspirin for elderly people with dysphagia.

The impact of demographic ageing is likely to be of major significance in the coming decades due to low birth rates and higher life expectancy. Older people generally require more prescribed medicines due to the presence of multiple conditions such as dysphagia which can make swallowing medicines challenging. This study involves the development, characterization and optimization of composite wafers for potential oral and buccal delivery of low dose aspirin to prevent thrombosis in elderly patients with dysphagia. Blank (BLK) wafers (no loaded drug) were initially formulated by dissolving combinations of metolose (MET) with carrageenan (CAR) and MET with low molecular weight chitosan (CS) in different weight ratios in water, to identify optimum polymer combinations. However, drug loaded (DL) wafers were prepared using 45% v/v ethanol to help complete solubilization of the aspirin. The formulations were characterized using texture analyzer (hardness, mucoadhesion), scanning electron microscopy (SEM), X-ray diffractometry (XRD), attenuated total reflectance - Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), thermogravimetric analyzer (TGA), and swelling capacity. Wafers with higher total polymer concentration were more resistant to penetration (MET:CAR 1:1 samples B2, C2) and MET:CS 1:1 (sample E2) and MET:CS 3:1 (sample F2) and also depended on the ratios between the polymers used. From the characterization, samples C2, B2, E2 and F2 showed the most ideal characteristics. XRD showed that BLK wafers were amorphous, whilst the DL wafers were crystalline due to the presence of aspirin. SEM confirmed the presence of pores within the polymer matrix of the BLK wafers, whilst DL wafers showed a more compact polymeric matrix with aspirin dispersed over the surface. The DL wafers showed a good flexibility required for transportation and patient handling and showed higher swelling capacity and adhesion values with phosphate buffer saline (PBS) than with simulated saliva (SS). Drug dissolution studies showed that aspirin was rapidly released in the first 20 min and then continuously over 1 h. FTIR confirmed the interaction of aspirin with the polymers evidenced by peak shifts around 1750 cm-1 and the broad peak between 2500 and 3300 cm-1. Lyophilized CAR: CS 1:3 (sample DL13), MET:CS 1:3 (sample DL8) and MET:CAR 3:1 (sample DL1) wafers seem to be a very promising system for the administration of low dose aspirin for older patients with dysphagia.

Composite Alginate-Hyaluronan Sponges for the Delivery of Tranexamic Acid in Postextractive Alveolar Wounds.

The management of wounds in patients on anticoagulant therapy who require oral surgical procedures is problematic and often results in a nonsatisfactory healing process. Here, we report a method to prepare an advanced dressing able to avoid uncontrolled bleeding by occluding the postextractive alveolar wounds, and simultaneously, capable of a fast release of tranexamic acid (TA). Composite alginate/hyaluronan (ALG/HA) sponge dressings loaded with TA were prepared by a straightforward internal gelation method followed by a freeze-drying step. Both blank and drug-loaded sponges were soft, flexible, and elegant in appearance and nonbrittle in nature. Scanning electron microscopy analysis confirmed the porous nature of these dressings. The integration of HA influenced the microstructure, reducing the porosity, modifying the water uptake kinetic, and increasing the resistance to compression. TA release from ALG/HA sponges showed a controlled release up to 3 h, and it was faster in the presence of HA. Finally, an in vitro clotting test performed on human whole blood confirmed that the TA-loaded sponges significantly reduce the blood clotting index by 30% compared with ALG/HA20 sponges. These results suggest that, if placed in a socket cavity, these dressings could give a relevant help to the blood hemostasis after dental extractions, especially in patients with coagulation disorders.

3D printed microneedles for insulin skin delivery.

In this study, polymeric microneedle patches were fabricated by stereolithography, a 3D printing technique, for the transdermal delivery of insulin. A biocompatible resin was photopolymerized to build pyramid and cone microneedle designs followed by inkjet print coating of insulin formulations. Trehalose, mannitol and xylitol were used as drug carriers with the aim to preserve insulin integrity and stability but also to facilitate rapid release rates. Circular dichroism and Raman analysis demonstrated that all carriers maintained the native form of insulin, with xylitol presenting the best performance. Franz cell release studies were used for in vitro determination of insulin release rates in porcine skin. Insulin was released rapidly within 30 min irrespectively of the microneedle design. 3D printing was proved an effective technology for the fabrication of biocompatible and scalable microneedle patches.

Nicotine stabilization in composite sodium alginate based wafers and films for nicotine replacement therapy.

Composite wafers and films comprising HPMC and sodium alginate (SA) were formulated for nicotine (NIC) replacement therapy via the buccal route. Magnesium aluminium silicate (MAS) was added in different concentration ratios (0.25, 0.5, 0.75) to stabilize NIC and its effect on mechanical properties, internal and surface morphology, physical form, thermal properties, swelling, mucoadhesion, drug content and release behaviour of the formulations was investigated. MAS changed the physico-mechanical properties of the composite formulations causing a decrease in mechanical hardness, collapsed wafer pores, increased roughness of film surface, increase in crystallinity and decreased mucoadhesion of the wafers. However, MAS increased swelling in both films and wafers as well as interaction between NIC and SA, which increased drug-loading capacity. Further, MAS resulted in rapid and slow release of NIC from wafers and films respectively. The results suggest that the ideal formulation for the stabilization of NIC in the composite formulations was MAS 0.25.