Introduction

1.1      Problem Overview

A problem in the pharmaceutical industry is that therapeutics are released from pills too quickly, which reduces the efficiency of the drug. The release of therapeutics can be controlled so that the therapeutics exit the hydrogel capsule over a sustained amount of time. The sustained release of therapeutics ensures that an effective dose (between the toxic and minimal effect thresholds - see figure 1) is administered to the consumer over a longer time period, thus raising the efficiency of the pill. Also, sustained therapeutic release decreases the amount of resources a pharmaceutical company uses because less therapeutics per pill are required.

Several design constraints need to be met for the project to be successful. One of the main goals is to reduce cost, so the total budget has to be cheap or below $100. The size of the capsules has to be small for human ingestion and a reasonable therapeutic diffusion rate; a size 22 needle is sufficient and produces spherical droplets with a nominal outer diameter of 0.72 mm. [1]

Figure 1: Chart describing the maximum toxic and minimum effect concentration threshold

1.2      Existing Solutions

Existing solutions for the therapeutic inefficiency include cross-linking alginate with various polymers to adjust physical properties of alginate, such as porosity, bead size, pressure resistance, and biodegradability. The rationale behind using alginate as a basis for hydrogels is because of its low toxicity, low cost, high bio-compatibility, and ease of gelation with different cations. Also, therapeutics can be easily encapsulated in hydrogels because of it is a quasi-solid matrix. Molecules used in conjunction with alginate includes calcium, magnesium, iron, chitosan, and PEG among many others. [2]

1.3      Project Objectives

    The primary goal of this project is to control therapeutic release by adjusting the structure of the alginate hydrogel. Ideally, the therapeutics will be released at a rate so that it stays within the effective threshold for the longest amount of time, which maximizes the pill’s efficiency. The project’s secondary goal is to achieve a remote control or chemical stimuli for therapeutic release. The desired outcomes include an alginate hydrogel capsule restructured for sustained therapeutic release, and a chemical mechanism or device that enables remote therapeutic release from the capsule.

    The final product is a chitosan-coated alginate hydrogel bead that is used to encapsulate and release therapeutics at a sustained rate. Chitosan is significantly less porous than alginate, and permits the transport of small macromolecules unlike the latter. Any larger molecules would not be able to diffuse through the chitosan pores. Chitosan, having a pKa of ~ 6.5, dissociate in only acidic environments and near mucous membranes, which enable transport of therapeutics to specific parts of the human body, such as the stomach, kidneys, or bladder without premature release. [2] Prior to arriving at an acidic environment, the chitosan-alginate hydrogel maintains its structure because chitosan does not break apart from the hydrogel in a neutral or basic environment; pH is the stimuli for hydrogel degradation and therapeutic release. Unlike existing solutions, the chitosan and alginate are not completely cross-linked to form a solid precipitate. Rather, they are layered so that calcium alginate retains its properties, while chitosan provides additional benefits.