How Formulators Can Incorporate Pharmaceutical Delivery Technologies

How Formulators Can Incorporate Pharmaceutical Delivery Technologies

by Stephen Turner

For many years, formulators have employed various methods and concepts tooptimize efficacy, performance and compliance when it comes to takingmedications. Often, the active ingredient dictates the final formulation butwhen market and sales factors are added to the mix, it is up to the formulatorto determine the most appropriate delivery vehicle. An appropriate, uniquedelivery option can differentiate a product in its market niche. If the productdoes not sell, regardless of the benefits, it will languish and eventually belost. By making use of technologies familiar to the pharmaceutical industry,formulators in the nutritional industry can utilize an impressive arsenal oftools available to provide an end product that can and will flourish within themarketplace.

Of all the ways to get a compound into the body, the oral route is the mostpreferred and offers the highest degree of consumer compliance. Tablets,capsules, sachets, chewable wafers and powdered preparations are among theoptions. Tablets and capsules are the most common solid oral dose in theindustry and can effectively deliver the intended dose. Ultimately, the materialsphysical properties, chemical properties and oral bioavailability determinewhether the active ingredient is appropriate for a tablet or capsule. If thetotal volume required is high, beyond two grams, a sachet orbulk powder is the logical course of delivery. It would be difficult to justifya tablet or capsule formulation knowing it would require consuming a largenumber of pills at any given time. Large dosing volumes or multiple dosingreduces consumer compliance and limits the marketability of the end product.Nutraceuticals and natural therapies that require reasonable amounts, below 2 grams, should consider the tablet or capsule form.

Familiarity with technologies and practices that are widely accepted withinthe pharmaceutical industry can help formulators achieve success in the area ofsolid oral dosage form design with products that provide unique and improvedperformance over conventional preparations and differentiate themselves from thecompetition. There are several major classes of technologies that allow forcontrolled delivery. Each type has its advantages and disadvantages, dependingon the design and release profile it was intended to achieve.

Drug delivery systems have evolved from candy coatings with the drug mixedinto the coating to the combination of physical and internal concepts that allowfor targeted and precise delivery within the human body. Whether designing forgastric bypass, site specific, bimodal, linear or specific needs for optimalabsorption or reducing side effects, a formulator can achieve virtually anythingby incorporating modern drug delivery technologies.

Delivery Systems

Simple matrix delivery systems incorporatehydrophilic polymers that swell in the presence of water or other inertmaterials such as waxes to control the release of the active components from thetablet or capsule. These technologies have been well utilized for more than 40years in the pharmaceutical industry. Simple matrix systems revolve around thecommon principle of diffusion suppression. This is also their limiting factor.The active ingredients need to be materials that can diffuse out of the tabletor capsule in order to engineer a level of control that can be reproduced. Thelongevity of these systems in the market affords formulators a pool of previousexamples from which to learn. For the nutritional industry, these types oftechnologies offer controlled release in a simple and cost effective manner butare limited to select compounds and often cannot provide patent protection onthe raw material itself. When considering this type of technology,differentiation in the marketplace can be difficult to attain due to thecapabilities of these systems and their longevity in the marketplace.

Multiparticulate delivery systems have diverse variationsbut can be generalized under one common principle. Multiparticulate systems area plurality of granules or micro spheres that can be loaded into either acapsule or tablet. Each of the beads is sorted for a characteristic rateof disintegration. By combining a variety of release rates into a single unitdose, a unique product can be designed. Multiparticulate systems offerformulators many different options and release profiles to meet nearly anydesired outcome. Unique and novel systems can offer patent protection to theproducts that incorporate these types of systems and can offer both atechnological advantage as well as product differentiation. Multiparticulatesystems are quite complex, adding significantly to the cost of design andmanufacture. Often, a multiparticulate system may even require specializedequipment, further increasing manufacturing costs. Variations in the surface andcoating thickness can also translate to incomplete release of the activeingredients--one shortcoming of this type of technology. Multiparticulatesystems also have difficulties handling large active ingredient loads, which canlimit the potential applications to compounds that are potent or require lessthan a few hundred milligrams of material in a single dose.

Even with the limitations on drug load, process variability and complexity,formulators in the nutritional industry use multiparticulate systems becausethey suit many types of materials. A formulator needs to closely weigh thedecision factors for a product when looking at this type of technology. If themarket cannot support the added costs to develop and manufacture this type ofproduct, alternative technologies may need to be considered. Complexity andcapabilities set multiparticulate delivery systems apart from othertechnologies; this is what also limits this technology in markets where price isan issue.

Osmotic pumps and other reservoir-styledelivery systems are another type of technology that has done very well in thepharmaceutical industry. These systems offer unique characteristics and truerate-limited release for high levels of control and precision but require veryspecialized and expensive manufacturing processes and equipment. The elementaryosmotic pump is built around a single or double-layered tablet that has anosmotic core. This specialized tablet is then coated with a semi-permeablemembrane that is designed to allow water in to hydrate the tablet core, whichswells and pushes its contents out through an orifice that is bored by a laser.Due to the cost and complexity of these systems, they are often not seen inmarkets that are sensitive to price, such as the over-the-counter (OTC) andnutritional industries. Reservoir-style delivery systems face similarlimitations to the multiparticulate system. Drug load, processing variabilityand loss combined with complexity and cost limit this type of technology tospecific compounds and markets.

An experienced formulator could physically or geometrically alter the dosageform to control delivery of its contents. Some recent examples of thesephysical-geometrical systems have been very impressive and canoffer very unique release profiles and easy patent enforcement. The drawbacks tophysical-geometrical systems are in the specialized equipment and processes ittakes to manufacture the dosage forms. So far, these types of technology havenot been very successful in proving robust, have fallen short on durability andmay show variability within the body. Once again, complex versions of this typeof technology do not lend themselves to the natural products industry due tocost and complexity. Simple physical alterations however, are seen in someproduct applications and can offer product differentiation for those productlines that can support the cost of this technology.

Controlled delivery mechanisms that combine the advantagesof the complex and intricate delivery systems with the ease and cost of firstgeneration technologies may have a distinct advantage. For example, TempleUniversity developed a patented self-correcting matrix style technology. Thepatent has been assigned to Nutraceutix, which has a platform of patentedtechnologies that can be applied to a variety of compounds. By incorporatingprinciples from the first generation of technologies previously described andovercoming their disadvantages, these self-correcting systems can achievemany of the same results as the current high cost and complex systems yet do itin a simple and cost effective manner. One example under this platform is U.S.Patent No. 6,090,411, which utilizes an electrolyte within a directly compressedmonolithic tablet to correct for the changes in diffusion and hydration rate andachieve linear release with very low excipient load. By utilizing this newstate-of-the-art technology, a formulator can offer high-end control at costsacceptable to the industry and capture a good portion of the available marketsegment. Controlled delivery technologies also allow a formulator or company toprotect their product in a highly volatile and price sensitive market. Thetechnologies also enhance the science behind the product to furtherdifferentiate it from unprotected immediate release forms that incorporate agiven raw material, reducing or eliminating potential market erosion.

By borrowing technology, expertise and experiences from the pharmaceuticalindustry, a nutritional formulator can offer unique and high-performanceproducts for the consumer. These differentiated products will have longer lifecycles in volatile markets and have higher sustainable gross margins whencompared to products lacking intellectual or scientific protection.

Stephen Turner, director of product development at Nutraceutix Inc., isresponsible for the companys research and development efforts, and isinstrumental in the application of proprietary delivery technologies for dietarysupplements, OTC and pharmaceuticals. He is an active member of AAPS as well asthe Controlled Release Society.