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

Abstract

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.

Development of a Mucoadhesive Vehicle Based on Lyophilized Liposomes for Drug Delivery through the Sublingual Mucosa

“…The liposome potential for permeation through the buccal epithelium was evaluated This assumption applies only to early samples due to cholesterol autoxidation in aqueous media. This explains the profile of the cumulative curves showing a descending phase after 4 h. Non-enzymatic oxidation of cholesterol in different sample types was reported [42], and this is one reason that justifies the interest in liposomal formulations being lyophilized for long-term stabilization.…”

Development and evaluation of bioadhesive buccal films based on sodium alginate for allergy therapy

“…In addition, many additives can be applied in polymer films, such as solvents, taste-masking agents, permeation enhancers, saliva-stimulating agents, etc. [ 18 , 19 , 20 ].…”

Composite Fish Collagen-Hyaluronate Based Lyophilized Scaffolds Modified with Sodium Alginate for Potential Treatment of Chronic Wounds

“…3 g of the prepared gel was poured into each mold of twelve-well plates (diameter 22.1 mm) (Thermo Fisher Scientific, Leicester, UK). The gels were freeze-dried in a Virtis Advantage XL 70 freeze dryer (Biopharma Process Systems, Winchester, UK), using an automated freeze-drying cycle as previously reported [16]. The samples were cooled from room temperature to 5 • C for 30 min, 5 • C to −5 • C for 1 h, and −5 • C to −50 • C for 3 h. Furthermore, an annealing step was incorporated in the freezing step to enhance the pore size distribution by increasing the temperature from −55 • C to −25 • C for 2.5 h and cooling it back to −55 • C for 3 h. In the primary drying stage, a pressure of 50 mTorr was applied and the temperature was increased from −55 • C to −25 • C for 12 h and further increased from −25 • C to +20 • C for 7 h. The same pressure was applied during secondary drying and the temperature was held at +20 • C for 6 h to remove the remaining residual moisture [16].…”

“…As previously reported by Álvarez-Suárez and colleagues [44] the amount of exudate produced by a patient with a burn wound is ~5000 g/m 2 /day, while exudate production for chronic ulcers ranges from 4000 to 12,000 g/m 2 /day. Therefore, formulations in this study with WVTR ranging from 2527 ± 38 to 2405 ± 69 are capable of transmitting about 50% exudate from burn and mild exuding chronic wound bed [16,45]. This implies that the composite SA:FCOL:HA scaffolds will be able to provide a moist environment to enable the progression of wound healing, whilst preventing the collection of excess exudate, which could cause maceration of healthy skin around the wound as well as prevent the possibility of infection developing.…”