Joshua S. Boateng

Advanced Therapeutic Dressings for Effective Wound Healing-A Review.

Advanced therapeutic dressings that take active part in wound healing to achieve rapid and complete healing of chronic wounds is of current research interest. There is a desire for novel strategies to achieve expeditious wound healing because of the enormous financial burden worldwide. This paper reviews the current state of wound healing and wound management products, with emphasis on the demand for more advanced forms of wound therapy and some of the current challenges and driving forces behind this demand. The paper reviews information mainly from peer-reviewed literature and other publicly available sources such as the US FDA. A major focus is the treatment of chronic wounds including amputations, diabetic and leg ulcers, pressure sores, and surgical and traumatic wounds (e.g., accidents and burns) where patient immunity is low and the risk of infections and complications are high. The main dressings include medicated moist dressings, tissue-engineered substitutes, biomaterials-based biological dressings, biological and naturally derived dressings, medicated sutures, and various combinations of the above classes. Finally, the review briefly discusses possible prospects of advanced wound healing including some of the emerging physical approaches such as hyperbaric oxygen, negative pressure wound therapy and laser wound healing, in routine clinical care.

Taste masking of paracetamol by hot-melt extrusion: An in vitro and in vivo evaluation

The purpose of this study was the in vitro and in vivo evaluation of the masking efficiency of hot melt extruded paracetamol (PMOL) formulations. Extruded granules containing high PMOL loadings in Eudragit EPO (EPO) or Kollidon VA64 (VA64) were prepared by hot-melt extrusion (HME). The taste masking effect of the processed formulation was evaluated in vivo by a panel of six healthy human volunteers. In addition, in vitro evaluation was carried out by an Astree e-tongue equipped with seven sensors. Taste sensing technology demonstrated taste improvement for both polymers by correlating the data obtained for the placebo polymers and the pure APIs alone. The best masking effect was observed for VA64 at 30% PMOL loading. The e-tongue results were in good agreement with the in vivo evaluation. In vitro dissolution of the extruded granules showed rapid PMOL releases.

A Review of Hot-Melt Extrusion: Process Technology to Pharmaceutical Products

Over the last three decades industrial adaptability has allowed hot-melt extrusion (HME) to gain wide acceptance and has already established its place in the broad spectrum of manufacturing operations and pharmaceutical research developments. HME has already been demonstrated as a robust, novel technique to make solid dispersions in order to provide time controlled, modified, extended, and targeted drug delivery resulting in improved bioavailability as well as taste masking of bitter active pharmaceutical ingredients (APIs). This paper reviews the innumerable benefits of HME, based on a holistic perspective of the equipment, processing technologies to the materials, novel formulation design and developments, and its varied applications in oral drug delivery systems.

Preparation, optimisation and characterisation of novel wound healing film dressings loaded with streptomycin and diclofenac

Streptomycin (STP) and diclofenac (DLF) loaded film dressings were prepared by blending Polyox(®) (POL) with four hydrophilic polymers [hydroxypropylmethylcellulose (HPMC), carrageenan (CAR), sodium alginate (SA) or chitosan (CS)] using glycerol (GLY) as plasticiser. The films were characterised by scanning electron microscopy (SEM), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy, texture analysis (tensile and swelling characteristics) and in vitro dissolution profiles using Franz diffusion cell. SEM showed homogeneous morphology for both blank (BLK) and drug loaded (DL) films. Films prepared by blending of POL with the other polymers showed a reduction in the crystallisation of POL in descending order of SA>CS>HPMC>CAR respectively. DSC and XRD showed no crystalline peaks of STP and DLF suggesting molecular dispersion of both drugs as well as possible drug interaction with negatively charged sulphate ions present in CAR. The DL films did not show any IR bands of both drugs, confirming the DSC and XRD results. POL-CAR-BLK films showed higher tensile strength (12.32±1.40 MPa) than the POL-CAR-DL films (9.52±1.12 MPa). DL films plasticised with 25%w/w GLY revealed soft and tough (tensile strength 1.02±0.28 MPa, % elongation 1031.33±16.23) formulations. The swelling capacities of POL-CAR-BLK and POL-CAR-DL films were (733.17±25.78%) and (646.39±40.39%), increasing to (1072.71±80.30%) and (1051±86.68%) for POL-CAR-BLK-25% GLY and POL-CAR-DL-25% GLY respectively. POL-CAR-DL films showed significantly (n=3, p<0.0318) lower cumulative release of STP and DLF (52.11±1.34, 55.26±2.25) compared to POL-CAR-DL-25% GLY films (60.07±1.56, 63.39±1.92) respectively.

Characterisation of freeze-dried wafers and solvent evaporated films as potential drug delivery systems to mucosal surfaces.

Freeze-dried (lyophilised) wafers and solvent cast films from sodium alginate (ALG) and sodium carboxymethylcellulose (CMC) have been developed as potential drug delivery systems for mucosal surfaces including wounds. The wafers (ALG, CMC) and films (CMC) were prepared by freeze-drying and drying in air (solvent evaporation) respectively, aqueous gels of the polymers containing paracetamol as a model drug. Microscopic architecture was examined using scanning electron microscopy, hydration characteristics with confocal laser scanning microscopy and dynamic vapour sorption. Texture analysis was employed to investigate mechanical characteristics of the wafers during compression. Differential scanning calorimetry was used to investigate polymorphic changes of paracetamol occurring during formulation of the wafers and films. The porous freeze-dried wafers exhibited higher drug loading and water absorption capacity than the corresponding solvent evaporated films. Moisture absorption, ease of hydration and mechanical behaviour were affected by the polymer and drug concentration. Two polymorphs of paracetamol were observed in the wafers and films, due to partial conversion of the original monoclinic to the orthorhombic polymorph during the formulation process. The results showed the potential of employing the freeze-dried wafers and solvent evaporated films in diverse mucosal applications due to their ease of hydration and based on different physical mechanical properties exhibited by both type of formulations.

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°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°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.

Development and physico-mechanical characterisation of lyophilised chitosan wafers as potential protein drug delivery systems via the buccal mucosa

Lyophilised wafers from chitosan have been developed as potential protein drug delivery systems via the buccal mucosa. Wafers were prepared by lyophilising aqueous gels of the polymer incorporating varying concentrations of glycerol as plasticizer and d-mannitol as cryoprotectant. The different formulations were characterised by their physico-mechanical properties in order to select the optimum system for further development. The optimised formulation with 6.5 mg each of both plasticizer and cryoprotectant was loaded with bovine serum albumin and lyophilised with or without annealing. Differential scanning calorimetry was used to determine the appropriate lyophilisation cycle by evaluating thermal events before lyophilisation and possible phase separation of bovine serum albumin after lyophilisation. Texture analysis was employed to investigate the in vitro mucoadhesive properties in tensile mode, residual moisture content by thermo-gravimetric analysis while hydration capacity and drug release studies were performed in 0.1 M phosphate buffered saline. Microscopic architecture and crystallinity were examined using scanning electron microscopy and X-ray diffractometry respectively. The ease of hydration, in vitro mucoadhesive characteristics, microscopic architecture and BSA release were influenced by the annealing process. A 7 h cumulative percentage drug release of 91.5% and 80.1% was observed for the annealed and non-annealed wafers respectively. The results showed the potential of employing lyophilised chitosan wafers for buccal mucosa delivery of protein based drugs.

In vitro drug release studies of polymeric freeze-dried wafers and solvent-cast films using paracetamol as a model soluble drug

Drug dissolution and release characteristics from freeze-dried wafers and solvent-cast films prepared from sodium carboxymethylcellulose (CMC) have been investigated to determine the mechanisms of drug release from the two systems. The formulations were prepared by freeze-drying (wafers) or drying in air (films), the hydrated gel of the polymer containing paracetamol as a model soluble drug. Scanning electron microscopy (SEM) was used to examine differences between the physical structure of the wafers and films. Dissolution studies were performed using an exchange cell and drug release was measured by UV spectroscopy at 242 nm. The effects of drug loading, polymer content and amount of glycerol (films) on the release characteristics of paracetamol were investigated. The release profiles of paracetamol from the wafers and films were also compared. A digital camera was used to observe the times to complete hydration and dissolution of the wafers containing different amounts of CMC and how that impacts on drug release rates. Both formulations showed sustained type drug release that was modelled by the Korsmeyer-Peppas equation. Changes in the concentration of drug and glycerol (films) did not significantly alter the rate of drug release while increasing polymer content significantly decreased the rate of drug release from both formulations. The results show that the rate of paracetamol release was faster from the wafers than the corresponding films due to differences in their physical structures. The wafers which formed a porous network, hydrated faster than the more dense and continuous, (non-porous) sheet-like structure of the films.

Preparation and optimization of PMAA–chitosan–PEG nanoparticles for oral drug delivery

The objective of this study was to develop pH sensitive polymethacrylic acid-chitosan-polyethylene glycol (PCP) nanoparticles. This was achieved by dispersion polymerization of methacrylic acid (MAA), polyethylene glycol (PEG) and different chitosan (CS) grades in the presence of cross linking agent ethylene dimethacrylate (EDMA) and polymer initiator potassium persulphate. Method development was carried out by varying formulation parameters such as type of CS, ratio of PEG to CS, quantity of solvent and polymer initiator. Metoprolol (MTP) tartrate was incorporated into the nanoparticles (NPs) as a model drug. Laser diffraction, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) studies revealed that the NPs were spherical with smooth surfaces ranging in size from 190 to 450 nm. X-ray diffraction (XRD) and differential scanning calorimetry (DSC) findings showed the presence of amorphous MTP in PCP NPs. The MTP loading of PCP and glycol chitosan (GC) NPs varied from 10 to 45% depending on the CS grade while both types of NPs showed excellent binding efficiency on mucin from porcine stomach. The in vitro dissolution study showed pH dependent release profiles suggesting that the PCP NPs system have great potential for oral controlled drug delivery as an alternative to conventional dosage forms.

Development and functional characterization of alginate dressing as potential protein delivery system for wound healing.

This study aimed to develop and characterize stable films as potential protein delivery dressings to wounds. Films were prepared from aqueous gels of sodium alginate (SA) and glycerol (GLY) (SA:GLY 1:0, 1:1, 1:2, 2:3, 2:1, 4:3). Purified recombinant glutathione-s-transferase (GST), green fluorescent protein (GFP) and GST fused in frame to GFP (GST-GFP) (model proteins) were characterized (SDS PAGE, Western blotting, immune-detection, and high sensitivity differential scanning calorimetry) and loaded (3.3, 6.6 and 30.2mg/g of film) into SA:GLY 1:2 film. These were characterized using texture analysis, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), scanning electron microscopy, swelling, adhesion, dissolution and circular dichroism (CD). The protein loaded dressings were uniform, with a good balance between flexibility and toughness. The films showed ideal moisture content required for protein conformation (TGA), interactions between proteins and film components (DSC), indicating stability which was confirmed by CD. Swelling and adhesion showed that formulations containing 6.6mg/g of protein possessed ideal characteristics and used for in vitro dissolution studies. Protein release was rapid initially and sustained over 72h and data fitted to various kinetic equations showed release followed zero-order and Fickian diffusion. The results demonstrate the potential of SA dressings for delivering therapeutic proteins to wounds.