Composite sodium alginate and chitosan based wafers for buccal delivery of macromolecules.

The objective of this study was to develop a composite buccal wafer for protein drug delivery. The polymeric vehicle used in this study combined chitosan and sodium alginate with bovine serum albumin (BSA) as a model drug. The wafers were obtained by freeze-drying gels of the polymers in well plates. Prior to the lyophilisation process, differential scanning calorimetry was performed to establish a suitable freeze-drying cycle. Preliminary characterization experiments were undertaken to select the optimum composite gel containing sodium alginate and chitosan in a 4:1 ratio respectively for drug loading. A second series of characterisation tests were performed on the drugloaded wafers prepared from gels containing 0.25 and 0.5 % w/w of BSA. The formulations were functionally characterised for swelling, mucoadhesive and drug dissolution properties. The morphology and crystallinity were investigated using a scanning electron microscope and X-ray diffractometer respectively. The results from drug dissolution studies over a two-hour period showed 66% and 31% cumulative drug release for the wafers obtained from gels containing 0.25 and 0.50 % w/w BSA respectively. These results show the feasibility of developing a sustained delivery system for macromolecules by combining chitosan and sodium alginate

Erodible Film Formulation for Potential Ocular Drug Delivery

Drug delivery to the eye has always been an interesting and challenging field in pharmaceutical formulation and drug design. The aim of this research was the formulation development of thin erodible films for potential delivery of lopidine to treat glaucoma. Films were prepared using hyaluronic acid (HA) and hydroxypropyl methylcellulose (HPMC) as polymers, together with glycerol (GLY) as plasticiser. Single layer films were prepared using each polymer individually, as well as in combination to obtain composite thin films. Various combinations and concentrations were optimised to reach the desired transparency, which were then characterised for their physico-chemical and mechanical properties. The following ratios were selected for drug loading: 2% HPMC, 1% HA, 1% composite (HPMC 1:1 HA) and 2% composite (HPMC 1.5:0.5 HA) with all of them containing a ratio of 2:1 polymer to plasticiser

Composite bi-layered erodible films for potential ocular drug delivery

Bi-layered hydroxypropylmethylcellulose and Eudragit based films were formulated as potential ocular drug delivery systems using chloramphenicol as a model antibiotic. Films were plasticized with polyethylene glycol 400 present in the Eudragit layer or both Eudragit and hydroxypropylmethylcellulose layers, and loaded with chloramphenicol (0.5% w/v in solution) in the hydroxypropylmethylcellulose layer. The weight, thickness and folding endurance optimized formulations were measured and further characterized for transparency, tensile, mucoadhesive, swelling and in vitro drug dissolution properties. The physical form of chloramphenicol within the films was evaluated using differential scanning calorimetry (DSC), and X-ray diffraction (XRD), complimented with scanning electron microscopy and energy dispersive X-ray spectroscopy. Fourier transform infrared spectroscopy was used to assess the interactions between the drug and the film components and confirm chloramphenicol’s presence within the sample. Optimum films showed high transparency (≥ 80% transmittance), ease of peeling from Petri dish and folding endurance above 250. Average thickness was lower than contact lenses (0.4 - 1mm), confirming them as thin ocular films. The tensile properties showed a good balance between toughness and flexibility and mucoadhesivity showed that they could potentially adhere to the ocular surface for prolonged periods. The drug loaded films showed swelling capacity which was greater than 300% of their original weight. The physical form of chloramphenicol within the films was amorphous (DSC and XRD) whilst in vitro drug dissolution showed sustained drug release from the films for four hours, before complete erosion. The chloramphenicol loaded films represent a potential means of treating common eye infections

Development and evaluation of lyophilized thiolated-chitosan wafers for buccal delivery of protein

Annealed and non-annealed freeze-dried wafers from synthesised thiolated-chitosan have been developed and evaluated. Wafers were obtained by freeze-drying aqueous gels of the thiolated polymer incorporating per polymer weight, 10 % each of glycerol as plasticizer, D-mannitol as cryoprotectant and 50% BSA as model protein drug. The formulation was freeze-dried with or without the process of annealing. Texture analyzer was employed to investigate the in vitro mucoadhesive properties in tensile mode, residual moisture content by thermo-gravimetric analysis (TGA) while hydration capacity and drug release studies were performed in 0.1M PBS. Microscopic architecture was examined using scanning electron microscopy (SEM). Differential scanning calorimetry (DSC) was employed for protein phase separation studies and conformational stability by attenuated total reflectance-Fourier transform infra-red spectroscopy (ATR-FTIR) and confirmed with Circular dichroism (CD). The annealing process led to wafers with increased ease of hydration, improved in vitro mucoadhesive characteristics and enhanced BSA release, without affecting the conformational stability of the protein due to the presence of a cryoprotectant. These results show the potential application of annealed freeze-dried thiolated chitosan wafers for buccal mucosa delivery of protein based drugs

Novel lyophilization cycle development of chitosan based formulation for buccal delivery using paracetamol as a model drug

Purpose: To develop freeze dried chitosan formulations for buccal mucosa delivery and to determine the effects of plasticization and annealing on their physical properties. Method: 1g of chitosan (medium molecular weight) was dissolved in 50ml of 1% acetic acid and the pH adjusted to 6.5 with 5M NaOH added drop wise. 50ml aqueous solutions comprising mannitol (10%) as cryoprotectant, glycerol (0-50%) as plasticizer and paracetamol (10%) as a model drug were added to give homogeneous gels (1%) and stirred continuously at room temperature (1hour). The resulting gels were freeze-dried in a Virtis Advantage Freeze Dryer. Preliminary thermal characterization by DSC informed the selection of annealing temperature for the novel lyophilization cycle development. The process involved freeze treatment from room temperature to -55°C (2 hours), annealing to -35°C (2 hours) and finally freezing back to -55°C (2 hours). The wafers obtained were evaluated for flexibility, toughness, brittleness, residual water content by gravimetry (heating in an oven and TGA), micro-structure characterisation by SEM and hydration behaviour in aqueous dissolution medium. Results: Unplasticised wafers were brittle, easily broken along fractured surface (fig. 1a) and instantaneously disintegrated upon contact with dissolution medium whiles high content plasticized wafers collapsed during lyophilization. Optimized concentration of glycerol (10%) however produced flexible, tough and non-brittle wafers (fig. 1b). Annealing facilitated the removal of stresses and softened crystallisable materials thereby improving toughness and reducing brittleness. The mean (+s.d) residual water content of optimized wafers by both gravimetric approaches was 1.9% (+ 0.18) which is consistent with literature optimum range of 1.7 - 4%. The SEM evaluation showed micrographs of plasticized and annealed wafers with porous network which were morphologically stable (fig. 2). This is expected to affect their hydration and swelling behaviour and ultimately drug release characteristics.In addition to plasticizing, glycerol enabled the wafers to swell instead of instantly disintegrating when in they came into contact with dissolution medium. Conclusion: Stable freeze-dried chitosan wafers have been developed. Plasticization and annealing helped to achieve the desirable physical characteristics of these wafers

Preparation and optimization of PMAA-Chitosan-PEG nanoparticles for oral drug delivery

INTRODUCTION: In the current study pH sensitive polymethacrylic acid – chitosan–polyethyleneglycol (PCP) nanoparticles, were developed through a free radical polymerisation process [1]. Metoprolol was used as a model active substance and the obtained PCP nanoparticles presented excellent drug loading (20–30%) and bioadhesion properties

Preparation and characterization 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 plasticized 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

Design and formulation of a novel polymer-based buccal film

The aim of this work was to develop a novel film for delivering amorphous drugs into the systemic circulation via the buccal mucosa. The advantage of the buccal mucosa over the sublingual, such as better systemic effects, has led to its exploration as a functional administration route [1]. Buccal formulations can be developed as films, freeze- dried wafers [2] which are suitable alternatives to deliver drugs promptly and safely

Physico-chemical characterization of oral thin film for paediatric buccal drug delivery

Recent changes in regulatory requirements for paediatric formulations demand development of age-appropriate dosage forms that are stable for ease of dosing, compliance and dose flexibility while maintaining accuracy and safety. Films were developed by optimising various formulation variables including type of solvent (water, ethanol), polyethylene glycol (PEG 400) as plasticiser and different film forming polymers [(metolose (MET), hydroxypropylmethylcellulose (HPMC), methylcellulose (MC), sodium alginate (SA), and carrageenan (CA)], drug stabilization and loading capacity. Films were subsequently functionally characterised using various techniques