Papain entrapment in alginate beads for stability improvement and site-specific delivery: Physicochemical characterization and factorial optimization using neural network modeling

Abstract

This work examines the influence of various process parameters (like sodium alginate concentration, calcium chloride concentration, and hardening time) on papain entrapped in ionotropically cross-linked alginate beads for stability improvement and site-specific delivery to the small intestine using neural network modeling. A 3(3) full-factorial design and feed-forward neural network with multilayer perceptron was used to investigate the effect of process variables on percentage of entrapment, time required for 50% and 90% of the enzyme release, particle size, and angle of repose. Topographical characterization was conducted by scanning electron microscopy, and entrapment was confirmed by Fourier transform infrared spectroscopy and differential scanning calorimetry. Times required for 50% (T(50)) and 90% (T(90)) of enzyme release were increased in all 3 of the process variables. Percentage entrapment and particle size were found to be directly proportional to sodium alginate concentration and inversely proportional to calcium chloride concentration and hardening time, whereas angle of repose and degree of cross-linking showed exactly opposite proportionality. Beads with >90% entrapment and T(50) of <10 minutes could be obtained at the low levels of all 3 of the process variables. The inability of beads to dissolve in acidic environment, with complete dissolution in buffer of pH >or=6.8, showed the suitability of beads to release papain into the small intestine. The shelf-life of the capsules prepared using the papain-loaded alginate beads was found to be 3.60 years compared with 1.01 years of the marketed formulation. It can be inferred from the above results that the proposed methodology can be used to prepare papain-loaded alginate beads for stability improvement and site-specific delivery.

Enteric Microsphere Formulations of Papain for Oral Delivery

“…Available studies where papain was immobilized in ionotropically crosslinked sodium alginate and kappa-carrageenan gel beads reported that 90％ of papain was released from formulation within 50 minutes in simulated gastric ‰uid. 22,23) As a result papain would remain almost inactive as well as lose its structural integrity at low pH of stomach (pH 1.2). Hence su‹-cient amount of papain would not reach to the target site for digestion of peptides/proteins.…”

Design and Development of Gliclazide Mucoadhesive Microcapsules: In Vitro and In Vivo Evaluation

“…The added droplets were retained in the calcium chloride solution for 15 min to complete the curing reaction and to produce spherical rigid microcapsules. The time of gel formation influences the drug loading efficiency and also the cohesion of the gel (17). The drug loading efficiency as a function of microcapsules formation time (time of contact with CaCl 2 solution) is reported in Fig.…”

Preparation and Characterisation of Phenytoin-Loaded Alginate and Alginate-Chitosan Microparticles

“…Figure 5 depicts the phenytoin release profiles from all alginate and alginate-chitosan microparticle formulations manufactured in the one-stage procedure. The times for 50% and 90% of drug to be released (t 50% and t 90% , respectively), as the parameters suitable for comparing the different formulations (Takka and Acarturk 1999;Sankalia et al 2005), are shown in Table 3. We found that the influence of chitosan coating on phenytoin release cannot be clearly deduced.…”