Intelligent Drug Delivery Technologies: An outlook

Currently, the focus has been on novel or innovative drug delivery technologies that are intelligent enough to navigate the therapeutic molecule to the desired site, quickly and economically, say Vivek Ranjan Sinha, Jayant Rajaram Bhinge and Aman Trehan

The advent of biotechnology and near completion of human genome project has resulted in a number of novel drugs along with new protein-based therapies. But because of their proteinaceous nature, conventional routes fail to deliver them to accurate/targeted site for proper duration of action. To overcome their delivery challenges, various new technologies have been developed, and some are under development.

Drug delivery technologies should not just extend patent life but enable difficult-to-deliver compounds as well as offer improved efficacy, safety, and patient compliance to existing drugs. Because of the targeting characteristics of some technologies, smaller amounts of drug are required to achieve the appropriate concentration at a specific site, hence, a reduction in side effects.

Oral controlled release

The oral route is the most popular and preferred route used for controlled delivery of drugs because of convenience, ease of administration, and flexibility in dosage form design. The drug can be administered for local as well as for systemic effects. Using this conventional dosage form, drugs are sometimes unable to achieve steady-state plasma concentrations; therefore, the problem of over- or under- medication may occur.

Add poor patient compliance to this, and the risk of adverse effects increases. These challenges can be addressed with controlled drug delivery systems that provide several advantages, such as the drug being delivered at a predetermined rate for specific period of time and at specific site, reduced frequency of administration, reduced side effects, improved patient compliance, increased safety margin of highly potent drugs, reduced healthcare costs, and improved therapy. The following is by no means a complete list, but an insightful overview.

Micropump

This technology is used for oral controlled release ranging from pediatric to geriatric uses and consists of multiple dose stems, containing 5,000 to 10,000 microparticles per capsule or tablet. Micro particles having a diameter of 200 to 500 mm are released in the stomach and then pass into the small intestine.

Upon coming in contact with the small intestine, each microparticle acts as a miniature delivery system and releases the drug by osmotic pressure at an adjustable rate.

Programmable oral release technologies

The Programmable Oral Release Technologies (PORT) delivery system is a novel capsule-based system. One or more drugs are incorporated in a single dosage form, which is capable of delivering one or more timed doses. The PORT delivery system is a major advancement in oral drug delivery and is applicable to a wide variety of drug classes (see figure 1).

Two water-insoluble drug technologies have been developed by the company. The first technology is a novel water-soluble pharmaceutical coating based on lecithin and gelatin that enhances both the rate and the extent of dissolution of poorly water-soluble drugs. The second technology is a novel micro-emulsion drug delivery system that improves the bioavailability of water-insoluble drugs over other microemulsion systems.

Oros

ALZA Corporation pioneered the transformation of the standard pharmaceutical tablet into an advanced drug delivery system with its OROS osmotic technology — technology incorporated into 13 commercialised products marketed around the world.

OROS uses osmosis as the driving force to provide precise, controlled drug delivery for up to 24 hours and can be used with a range of compounds, including poorly soluble or highly soluble drugs. OROS consists of an osmotic core containing drug and osmogen surrounded by semipermeable membrane, and an orifice (0.4 mm) created mechanically or with laser beam. It can be used to deliver high drug doses meeting high drug loading requirements.

Gastric retention system

The Gastric Retention (GR) system is the foundation on which all of Depomed’s technologies are built. It is well known that many drugs are best absorbed in the stomach and upper reaches of the small intestine. GR tablets are the only tablets on the market that will deliver substantially its entire drug payload to these upper GI sites.

The GR tablets sit safely and neutrally in the stomach for six, eight or even more hours and deliver drug at the desired rate, at the desired time. GR tablets can also be tailored to deliver exciting new drug combinations, of varying properties, either simultaneously, or sequentially, for a virtually endless array of product possibilities.

TIMERx

The TIMERx Technology from Penwest is a versatile, oral drug delivery platform that maximises a drug’s therapeutic value and product life. This oral drug delivery platform has a proven track record with dfficult actives such as high dose and insoluble compounds.

TIMERx platform technology is based on an agglomerated hydrophilic matrix. The matrix consists of two pharmaceutically accepted polysaccharides, locust bean gum and xanthan gum. Interactions between these components in an aqueous environment form a tight gel with slowly eroding core.

This system controls the rate of water ingress into the matrix and the subsequent diffusion and release of the drug from the dosage form.

Parenteral delivery

Parenteral route is the preferred route of administration with some drugs like proteins, where degradation occurs in GIT after oral administration. Nowadays various parenteral drug delivery technologies have been developed which provides slow, constant and sustained release of drug over prolonged period of time essentially to simulate and replace the more hazardous, continuous intravenous infusion of drug. Controlled parenteral delivery can be achieved through various novel technologies, few of which are discussed briefly.

DepoFoam technology (Skye pharmaceuticals)

DepoFoam drug delivery system provides a highly versatile technology that addresses many of the limitations associated with traditional methods of injectable drug administration, including side effects, drug concentration in the therapeutic window for a short period of time, poor patient compliance and high cost due to frequent administration.

Prolease and Medisorb (Alkermes Inc)

Alkermes has developed two uniquely complementary platforms for drug delivery: ProLease and Medisorb injectable sustained-release technologies for both small and macromolecules. With release profiles lasting from days to months, each is designed to eliminate the need for frequent dosing.

Each has the potential to improve patient compliance and convenience by reducing dosing frequency, improve safety and tolerability, reduce adverse effects associated with peak/trough levels of other (oral) dosage forms, commercialise products that would otherwise not be viable because of delivery or economic considerations and optimise product lifecycle management. Each technology supports a broad array of applications and offers customisable release profile lasting from days to months.

Needle free injection technology (Bioject) Bioject’s needle-free injection technology works by forcing liquid medication at high speed through a tiny orifice that is held against the skin. The diameter of the orifice is smaller than the diameter of a human hair.

This creates an ultra-fine stream of high-pressure fluid that penetrates the skin without using a needle. Bioject’s technology is unique because it delivers injections to a number of injection depths and supports a wide range of injection volumes.

For instance, the Biojector 2000 can deliver intramuscular or subcutaneous injections up to 1 mL in volume.

Needle-free injection technology has many advantages over needle-and-syringe injection methods which include; preferred by patients, improved efficacy, and versatility. Bioject’s needle-free injection systems can virtually eliminate the risk of accidental needle stick injuries for healthcare workers administering injections as contaminated needle sticks can transmit HIV, hepatitis, and other blood-borne pathogens, and are a major concern throughout the healthcare industry.

Powderject (Powderject)

A specialised technology for injecting the vaccines through the stratum corneum into the epithelium. Powderject system painlessly delivers DNA vaccines to the skin in a dry formulation. It consists of gold-coated antigen, which is delivered directly into skin, or other target tissue using a burst of helium gas. 1-3 mm high-density gold particles can be delivered intra-cellularly and the particles with 20-70 mm are delivered extracellularly.

Various vaccines can be delivered using powderject technology. Delivering hepatitis B surface antigen with new adjuvants such as CpG oligonucleotides (CpG DNA) using Powderject technology showed better immunisation and it is safe, effective and efficient immunisation method. Arilvaxâ (Celltech) a single dose, live, attenuated vaccine for the prevention of yellow fever, launched in Europe, is based on Powderject technology.

(To be concluded)

The writers are with University Institute of Pharmaceutical Sciences, Punjab University, Chandigarh.

E-mail: vr_sinha@yahoo.com