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 reflection-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 minutes and then continuously over 1 hour. FTIR confirmed the interaction of aspirin with the polymers evidenced by peak shifts around 1750 cm-1 and the broad peak between 2500 to3300 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.

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 TM artificial barrier, EpiOral TM 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 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 minutes and then continuously over 1 hour. EpiOral TM had a higher cumulative permeation than porcine buccal tissue and Permeapad TM 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.

Abstract:Objectives The aim of this study was to develop mucoadhesive oral strips using hot-melt extrusion as a continuous manufacturing process. Methods Powder blends of ketoconazole, a water insoluble drug; either hydroxypropyl methylcellulose (HPMC) or soluplus (SOL), sorbitol (SRB) and magnesium aluminometasilicate (MAS) were extruded to manufacture thin strips with 0.5 mm thickness. The presence of the inorganic metasilicate facilitated smooth processing of the extruded strips as it worked as an absorbent directly impacting on the extensive mixing of the drug/excipients inside the extruder barrel. Key findings The use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry (DSC) and transmission X-ray diffraction (TXRD) analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy (SEM) and energy dispersive X-Ray (EDS) undertaken on the formulations showed a homogeneous drug distribution within the extruded strips. Conclusion The strips produced via continuous HME processing showed significantly faster release of KTZ compared to the bulk drug substance. Journal of Pharmacy and Key findingsThe use of MAS also favoured the rapid hydration, swelling and eventual disintegration of the strips. Differential scanning calorimetry (DSC) and transmission X-ray diffraction (TXRD) analysis revealed the existence of the amorphous drug within the extruded strips. Scanning electron microscopy (SEM) and energy dispersive X-Ray (EDS) undertaken on the formulations showed a homogeneous drug distribution within the extruded strips. ConclusionThe strips produced via continuous HME processing showed significantly faster release of KTZ compared to the bulk drug substance.