TECHNOLOGIES

INHALATION:

The search for improved routes of administration and the desire for non-invasive delivery methods for self-medication of chronic conditions represent opportunities for developers of inhalation drug delivery based products. We believe that inhalation drug delivery is the fastest, non-injectable route of administration for many therapeutic agents. This makes it a preferred route of administration when a fast onset of action is required. In addition, for products that are orally unstable or undergo significant first-pass-metabolism, such as opioids, inhalation is a preferred route of administration.

TAIFUN® Inhalation Technology

TAIFUN® is AKELA Pharma’s proprietary multi-dose dry-powder inhaler (DPI) The device combines an integrated and patented desegregation system (vortex-chamber) and a unique humidity control system (desiccant capsule inside the drug reservoir), resulting in highly efficient fluid dynamics. The patented LURUX® wet suspension formulation method ensures excellent powder homogeneity. It also minimizes the formation of amorphous particles within the powder formulation, and ensures prolonged stability. In contrast to most marketed DPI products, the mechanical robustness and flexibility of TAIFUN, its functional strength and adaptability coupled with a low manufacturing cost position it as a very attractive dry powder inhalation platform. Salbutamol TAIFUN, the first TAIFUN product, has been approved in ten European countries.
 
 Advantages of Our TAIFUN® Technology

We believe that our TAIFUN® technology provides a number of technical improvements and clinical benefits, compared to current leading inhaled drug delivery systems. In particular, TAIFUN® enables reliable and efficient delivery of pharmaceuticals into patients' lungs in a wide range of clinical and environmental conditions. We believe that the unique combination of strong technical performance and user friendliness offers a competitive product platform for a variety of inhaled drugs.

In contrast to competing inhaler technologies that are being used or developed for the pulmonary administration of systemically active drugs, the TAIFUN® inhaler is a simple, all mechanical, small device that is inexpensive to manufacture. Despite its relative simplicity, the TAIFUN® inhaler incorporates advanced technology as well as meeting the regulatory requirements of modern dry powder inhalers. In particular, it can be adapted for a variety of small molecule drugs, economically manufactured, and introduced into market segments where pricing is competitive.

 We believe that the key advantages of TAIFUN® technology are:

• advanced powder formulations with high physical and chemical stability;

• high lung deposition of active drug independent of inhalation flow rate;

• high resistance to humidity;

• dose uniformity and accurate dose metering complying with FDA requirements;

• modern style and ease of use; and

• flexible dosing to accommodate varying patient needs.

 
EDACS™ and CureCap™ Oral dosage technology

Industry analysts estimate that the cost of prescription opioid analgesic abuse in the United States alone during 2005 was $9.5 billion, including costs related to healthcare, the criminal justice system and the workplace. The reasons most often cited for this level of prescription drug abuse include: prescription drugs are easier to acquire than illicit drugs (particularly in rural and suburban areas); the use/abuse of prescription drugs is more socially acceptable than illicit substances; and the purity and dosage is predictable and consequently safer to use.

Drug abusers typically prefer opioid and stimulant formulations that provide rapid absorption of the drug in order to obtain a desired euphoric effect. Sustained release oral formulations are not ideally suited for abusers when used correctly, but abusers can bypass the sustained release features of current products by crushing and mixing them with alcoholic drinks or by crushing and snorting or dissolving and injecting the drug. As a result, there is an increasing need to introduce sustained release formulations resistant to these types of physical abuse.

A limited number of technologies/systems are currently under development to deter the abuse of controlled substances. EDACS™ and CureCap™ - formulation systems (patents pending) are solid oral dosage forms contributing a safety enhanced solution to this problem.

Advantages of Our EDACS™ and CureCap Technologies

 Our EDACS™ technology is a solid oral dosage form designed to deter abuse of controlled substances or other drugs and to address the growing problem of prescription drug abuse. It has the following features:

• EDACS and CureCap prevents alcohol induced dose-dumping and alcohol extraction by maintaining its sustained release characteristics in 40% alcohol for more than three hours;

• EDACS and cureCap is significantly harder than conventional oral dosage forms and, as a result, it is very difficult to crush or chew in an attempt to bypass the sustained release characteristics; and

• EDACS and CureCap prevents dissolution and injection since it contains polymers that form a viscous gel not miscible in water and alcohol

EDACS™ products are manufactured by the novel hot-melt extrusion processing of a homogeneously blended powder. The powder for extrusion can be formulated to yield tablets or capsules with drug release characteristics much like other controlled release oral drugs. EDACS™ products can be prepared with both hydrophobic (water insoluble) or hydrophilic (water soluble) drugs, in various sizes, shapes and colors with a wide range of sustained release profiles. We believe EDACS is ideally suited to sustained release opioid and stimulant formulations. It is our expectation that, if approved, abuse deterrent formulations will eventually be the technology of choice for extended release opioid and stimulant formulations.

PHARMAFILM™ Transmucosal and Transdermal Film Technology

Transmucosal and transdermal drug delivery are an emerging field with many opportunities. AKELA’s PharmaFILM® is a patented, bioadhesive, thin film for delivery to the buccal mucosa, gingiva, rectal, vaginal or dermal surfaces.  Current prototypes have demonstrated in vitro release times ranging from 15 minutes up to 24 hours and in vivo release times from 1 to 20 hours depending on the half life of the active therapeutic agent. The film can be produced in single or multiple layers, and is suitable for combination therapies.

PharmaFilm offers benefits in the delivery of drugs with poor oral bioavailability due to significant first pass metabolism, or GI-tract degradation, and for patients with difficulties swallowing.

The use of bio-adhesive films for drug delivery is a growing market with many potential opportunities for market differentiation. PharmaFilm™ is a patented bio-adhesive transmucosal film featuring significant improvements in processing parameters, increased range of candidate drugs, with a broader range of film formation materials and with enhanced inhibition of crystal growth and formation. PharmaFilm™ formulation and processing flexibility greatly increase the adaptability for application at a variety of transmucosal and transdermal sites.
 Advantages of Our PHARMAFILM™ Technology

PharmaFilm™ is an oral transmucosal drug delivery film that is placed on a mucosal or dermal surface. Key advantages of the film include:

• suitability for a wide variety of drugs;

• improved bio-availability for certain therapeutic ingredients;

• small size for improved patient compliance;

• convenience for patients with difficulty swallowing;

• local and systemic delivery;

• dose removal possibility in emergency situations; and

• excellent content uniformity