Lipocine is a leader in providing realistic drug delivery solutions for challenging drugs to the pharmaceutical industry through superior product offerings and discovery support. Distinguished drug delivery professionals, Drs. William Higuchi and Mahesh Patel, founded Lipocine in 1997. The Company has several issued patents and pending patent applications, and has validated its technology by completing preclinical and clinical studies for several of its products. Lipocine has developed a portfolio of propiretary products with enhanced performance attributes and is well positioned to commercialize its lead products in the near term. Lipocine offers value-added Product Line Extension options to companies for licensing and commercialization and has several revenue-bearing collaborations with pharmaceutical partners corroborating its business model. Drug Delivery Technology recently interviewed Dr. Mahesh Patel, Lipocine's Co-founder, President, and CEO, to discuss how this Salt Lake City-based company is effecting change in product development and drug discovery through its innovative technologies.

Q: What do you see as the most critical unmet drug delivery need? How does Lipocine fulfill this need?

A: In my opinion, patient-friendly delivery of challenging drugs is the most critical unmet need facing healthcare professionals. Recent advances in biotechnology and combinatorial chemistry have brought about extraordinary therapeutic advances, but are also presenting significant drug delivery challenges to the development of patient-friendly products. It is estimated that more than 40% of all drugs discovered have drug delivery limitations due to poor solubility or poor permeability. Patients, especially pediatric and geriatric patients, overwhelmingly prefer oral ingestion of their medicines. However, this most common and preferred route of administration is inadequately understood. In fact, lack of optimal oral delivery solutions for drugs with solubility and permeability limitations have led to products requiring invasive delivery or products with compromised performance that is highly variable or highly sensitive to food interactions. Drug discovery and development at pioneer companies are also hampered when a promising New Chemical Entity must be abandoned due to drug delivery challenges. Given the fact that it is extremely difficult to discover innovative drugs in a timely fashion, the conventional solutions to delivery problems for NCEs using chemical modification are often too expensive or may be too late. The bottom line is that superior oral absorption of challenging drugs must be achieved. Therefore, our current focus is on improving oral absoption of drugs with challenging solubility and permeability characteristics. Lipocine has used its core competencies in lipid bioprocessing, oral absorption, and colloid chemistry to develop lipid-based technologies that enable patient-preferred products with the best possible oral absorption.

Q: Why utilize lipids as the foundation of your science?

A: Like water, lipids are omnipresent and are generally considered to have physico-chemical properties opposite to water. If a drug hates water, it would be logical to see if it likes the opposite. In my opinion, our industry has been neglectful in considering only one side of the drug solubility problem, i.e., water solubility at the expense of ignoring lipid solubility. Moreover, most biological membranes are composed of lipids, and it is well known that lipids can facilitate solute transport through bio-membranes. Lipid is a "catch all" term for lipophilic materials that are often multi-species, with each lipidic molecule having its own unique characteristics and diverse functionalities. Likewise, most drugs are polyfunctional. Therefore, lipid-based drug delivery systems offer tremendous formulation opportunities. With a smorgasbord of diverse lipids and good understanding of drug characteristics, one can improve drug solubilization and transport to achieve optimal absorption through lipidic formulations.

Q: What is Lip'ral™? What does it do and how is it unique?

A: Lip'ral is our technology platform that enables optimal oral absorption of poorly water-soluble drugs. The Lip'ral technology also lends control of the drug delivery performance to the formulation, as opposed to erratic performance at the mercy of patient's physiological state or concomitant food intake. Given the diverse nature of poorly soluble drugs, no one lipidic composition would meet these drug delivery objectives for all drugs. Therefore, through a customized design approach for a given drug and its desired product attributes, Lip'ral enables us to develop compositions that best present a challenging drug to the absorption site for effective absorption. Traditional problems associated with convential products for poorly water-soluble drugs are poor bioavailability leading to high doses or numerous dosage form units per dose, extreme sensitivity to food content and timing, slow onset of action, and high interpatient variability in bioavailability leading to inconsistent performance and undesirable side effects. One traditional solubilization approach, the use of cosolvents, can lead to uncontrolled in vivo drug precipitation severely compromising effective drug absorption. Other conventional solid-state dissolution-enhancement approaches include particle augmentation, such as milling or micronization or nanosizing, and the use of amorphous drug dispersions. These classical approaches address only part of the problem (dissolution) and do so at the expense of increased manufacturing complexity. Lip'ral technology is based on a novel and comprehensive approach that takes into account the importance of the critical step in oral absorption -- transport through the aqueous boundary layer. With Lip'ral, we provide pragmatic solutions to overcome this "aqueous barrier," a breakthrough in oral drug delivery. Lipidic pro-micellar concentrates with high drug solubilization capacity are designed for each drug. The subject drug remains dissolved in the spontaneously formed "micellar carrier" upon contact with the physiological milieu, thereby completely eliminating what would otherwise be very slow dissolution. These stable "micellar carriers" are designed for optimal drug loading capacity and the best drug transport efficiency through the barrier layer. These carriers have significant advantages relative to other lipidic disperse phases due to their small size, high diffusivity, stability, graduated polarity, and rapid drug release. Moreover, their performance is unaffected by physiological factors and food or beverage intake, and does not require enzyme-assisted digestion or bile secretion for solubilization. Therefore, Lip'ral-based products obtain the most efficient absorption possible, leading to the fastest onset of action and the fastest apparent elimination. These factors can be extremely valuable attributes for certain therapeutics. Additionally, Lip'ral-based products consistently perform well with a potentially improved therapeutic profile because they have a lower dose requirement, are refractory to food content or meal timing, and have virtually none of the absorption-related interpatient variability in bioavailability. These novel Lip'ral attributes have been clinically validated for several unique Lipocine and partnered products. Another advantage of Lip'ral-based products is their use of bioacceptable excipients, and their ease of manufacture using basic conventional processes.

Q: What is Lip'ral™-SSR and how is this unique?

A: Traditional controlled-release technologies enable controlled delivery of water-soluble drugs. However, these technologies, when applied to poorly water-soluble drugs, almost always have a negative impact on the bioavailability and possibly on the efficacy as well due to inadequate solubilization and release, pH-sensitive solubility, and "absorption window" limitations. Clinically validated Lip'ral Synchronized Solubilizer Release (SSR) is an extension of the Lip'ral technology platform and superimpose's controlled-release aspects while preserving the solubilizing power and absorption improvement aspects of the Lip'ral technology. Lip'ral-SSR synchronizes the release of the poorly water-soluble drug and lipidic solubilizers to achieve controlled release of both agents and is ideally suited for drugs that require solubilization and controlled release. It is especially suited for basic drugs with low intrinsic aqueous solubility that tend to precipitate in the intestinal tract. The release profiles can be modulated for delayed, pulsatile, or sustained release for targeted site absorption or chronotherapeutics without compromising therapeutic bioavailability. Other advantes of Lip'ral-SSR technologies are the use of bioacceptable excipients and the use of conventional manufacturing processes that are easy to scale-up.

Q: Please describe Hydroance™.

A: Hydroance is our technology platform to enable oral delivery of highly water-soluble compounds, including macromolecules. Hydrophilic therapeutic agents exhibiting poor membrane transport properties present enormous challenges in drug delivery primarily due to their charge, size, and stability characteristics. In the absence of appreciable oral absorption, most current hydrophilic dugs must be delivered invasively. Hydroance customizes lipid-based carriers for the optimal presentation of the drug and absorption promoters to the absorption site, thus enabling absorption of the drug across the membranes of the intestinal tract. Hydroance is suitable for small polar organics, peptides, polysaccharides, peptido-mimetics, and potentially vaccines. Hydroance utilizes non-NCE and bioacceptable lipids in practical amounts and uses realistic dosage forms to enable oral delivery. Lipocine has validated the utility of Hydroance with polysaccharides and several partnered drugs, including peptides in rat, swine, and monkey models.

Q: What is LipidScreen? and how does it assist potential partners?

A: LipidScreen is a rapid and cost-effective screening program to identify strategies to overcome drug delivery problems and to "salvage" or "shelve" a challenging drug. It allows clients to determine if problems with their compounds have a good probability of being solved with Lipocine technology before significant capital is devoted to a development program. Our clients include venture-backed discovery companies seeking formulation assistance, specialty pharmaceutical companies seeking value-added products, and "Big Pharma" with NCE delivery issues or seeking line-extension options to retain and expand their market share beyond drug patent expiration.

Q: What benefits does Lipocine technology have for the end-user?

A: Patients, and for that matter our pharmaceutical development partners, demand convenient patient friendly products. Lipocine's partners can expect access to clinically validated proprietary technologies to enable faster and cheaper commercialization of superior products. These products may represent a substantial improvement over existing dosage forms for established drugs, and in some cases, these could potentially be approved rapidly through the 505(b)(2) route. So patients can expect to have products that are convenient, robust, safer and more efficient, yet do not impose lifestyle or dietary restrictions. Additionally, our NCE drug delivery support could increase drug discovery and commercialization success rates, leading to better and less-expensive therapies.

Q: What is Lipocine's current strategic focus?

A: Lipocine technologies can be applied to a new or established drug in any therapeutic category. However, Lipocine's current focus is on improving bioperformance of marketed drugs. These have lower development costs, higher success rates, and are faster to market. Our particular focus in this area is on products for cholesterol (lipid) management, diabetes, and metabolic and cardiovascular disorders. We also have on-going collaborations with strategic partners in areas outside of this current focus.

Q: To what do you attribute Lipocine's success? How can you compete with other drug delivery companies in this area?

A: Lipocine founders and the senior management team have distinguished scientific credentials combined with extensive technical and business experience in technology innovation, "cradle to market" product development, and administration of successful drug delivery start-ups. We attribute our success to our relentless focus on ascertaining market needs, rigorous problem definition, and identifying pragmatic solutions through "out-of-the-box" thinking. This approach has led to our cutting-edge, lipid-based technologies. We emphasize using the best possible and most comprehensive solutions, yet are still practical and simple from a regulatory standpoint. For example, we utilize non-NCE, bioacceptable excipients and conventional manufacturing techniques. By staying focused on our goals and being credible with our staff and partners in our execution, we minimize product development iterations. At Lipocine, we see problems and opportunities more efficiently than most, and come up with aggressive and realistic plans to implement solutions. Through judicious utilization of lipids, we at Lipocine are championing a paradigm shift in oral absorption technologies. By emphasizing lipid solubility and drug transport across the "aqueous barrier" we are generating superior fast-to-market, patient-friendly products, and expanding the "bulls eye" in drug discovery and development.

Source: Drug Delivery Technology Magazine 350 Main Road Montville, NJ 07045 Phone: (973) 299-1200 Fax: (973) 299-7937