We have many years' experience in the application of proprietary oral drug delivery technologies to improve the performance of drugs, and as part of a planned pharmaceutical life cycle management programme.

We have extensive experience in solving the many challenges of delivering the right dose of a drug to the right part of the gastrointestinal system for absorption at the right time and at the appropriate rate to achieve the desired therapeutic effect.

Geomatrix™ provides a customisable drug delivery platform for controlled release versions of orally available molecules. Geoclock™ allows for the timed release of drugs that is independent of food or pH. Our latest innovation, Soctec™, was developed for drugs that need to be retained in the stomach for an extended period of time to then be slowly released either for a local effect in the stomach or for absorption in the upper intestine.

 

Technical challenge

Our solution

Benefit

Product examples

Zero order release

Geomatrix™

Once or twice-daily dosing

Paxil CR™
Requip® Once-a-day
Coruno®
Xatral®/Uroxatral®

Biphasic release

Geomatrix™

Rapid onset followed by sustained duration

Diclofenac-ratiopharm® uno
Zyflo CR®

Controlled release of several drugs in a single tablet

Geomatrix™

Several drugs that need to be released at different times or different rates can be combined in a single dose form

Madopar® DR

Ascending profile

Geomatrix™

Absorption of drugs in the lower GI tract

Sular®


Multiple pulses

Geoclock™

Two or more pulses of drug release separated by periods of no release

Suitable for drugs having undesirable side effects that can be minimised at certain times of the day

 

Timed release

Geoclock™

The drug effect can be achieved at a pre-determined time after administration

RAYOS®/LODOTRA®
SKP-1041 
SKP-1052

Colonic delivery

Geoclock™

Delivery to the colon where absorption of specific drugs is high or for topical effect in the colon

 

Improved delivery in upper gastrointestinal tract

Soctec™

For local effect in the stomach or targeted delivery to the duodenum and jejunum where absorption of specific drugs is higher

 

Improved bioavailability and food effect

IDD®
DissoCubes™

Improvement of bioavailability of BCS II and BCS IV drugs

Triglide®

Buccal delivery

Medicated chewing gum

Buccal absorption for improved systemic delivery or local effect

 

 

Geomatrix

Geomatrix™ is a well established, validated and customisable oral drug delivery platform technology that is currently used in eight products that are available in over 80 countries. Geomatrix™ is highly versatile and can be applied to a wide range of different drugs to achieve a variety of different release profiles. It uses well established ingredients and is easily manufactured using conventional production equipment.

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How Geomatrix™ works

Modulation of the drug release profile is achieved by using a multi-layered tablet that combines two key features:

  • use of highly swellable hydrophilic polymers (e.g. HPMC); and
  • dynamic control of the surface of the layer containing the drug that is exposed to surrounding fluids.

The combination of layers, each with different rates of swelling, gelling and erosion, controls the drug release rate within the body. When swallowed the Geomatrix™ system limits the amount of drug released by controlling the surface of the drug-containing layer exposed to fluids. As time progresses the core swells and the surface area increases to compensate for the decrease in drug concentration. The characteristics of Geomatrix™ can be adjusted very flexibly and reproducibly to the desired release properties.

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Benefits of Geomatrix™

Geomatrix™ is a highly versatile platform that can be used to create a wide variety of different release profiles. Examples of the application of Geomatrix™ include:

  • controlled release of both poorly and highly soluble drugs;
  • zero order and biphasic release of drugs (either rapid then slow or ascending profiles);
  • release of two or more drugs at different rates; and
  • simultaneous or phased release of several drugs at individualised release rates from a single tablet.

Geomatrix™ is currently used in eight products that are available in over 80 countries. It uses widely approved Generally Recognised as Safe (GRAS) inert ingredients and is easily manufactured using conventional production equipment.

Products incorporating Geomatrix™

Geomatrix™ technology is used in eight different products sold in more than 80 different countries, including:

Madopar DR, Paxil CR™, Requip Once-a-day, Xatral/ Uroxatral, Sular, Zyflo CR, Coruno™ and Diclofenac-ratiopharm uno.

Geoclock

Geoclock™ is a validated oral drug delivery technology that can be used to release the drug from the tablet after a predetermined lag time that is independent of food or pH. Geoclock™ can additionally be used for multiple pulse delivery of one or more drugs with predetermined time intervals between the pulses, or to target the colonic release of drugs. Where more than one drug is included, the delivery profile can be different for each active pharmaceutical ingredient. Geoclock™ is easily manufactured using conventional production equipment, minimising the need for capital investment.

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How Geoclock™ works

Geoclock™ is a dry-coated tablet with an active drug core inside an outer tablet layer comprising a mixture of hydrophobic wax and brittle material. This configuration generates a pH-independent lag time prior to the release of the active drug. After the pre-defined and configurable lag time the inner tablet releases the active drug either as a burst or with a controlled release pattern. The controlled release characteristics of the inner core can be modified to achieve the desired profile.

Benefits of Geoclock™

Geoclock™ can be used to create chronotherapy-focused drug delivery that is independent of the location in the GI tract, pH or food. Examples of the application of Geoclock™ include:

  • a burst release after a long lag time or a slow release rate after a short lag time;
  • drug delivery specifically at the colonic level, which is valuable for drugs targeted for colonic absorption; and
  • multiple pulse release e.g. to mimic multiple daily dosing of conventional formulations.

Geoclock™ is a validated technology that has been incorporated into products that are approved and on the market in the US and Europe. Tablets can be manufactured using standard tableting equipment, minimising the need for additional capital investment.

Products and projects incorporating Geoclock™

Geoclock™ has been incorporated into products that are approved and on the market in the US and Europe, and to the following products in development:

RAYOS®/LODOTRA, SKP-1041 and SKP-1052.

Bioavailability enhancers

We have a range of oral drug bioavailability enhancers that use proprietary technologies that act by improving solubility.

Solubility is an essential factor for drug effectiveness, independent of administration route. It is also a major challenge for pharmaceutical companies developing new products, since nearly half of all new chemically derived drugs are poorly soluble. Therefore, many promising compounds never reach the market or are developed in a sub-optimal formulation, providing low or unpredictable bioavailability or posing an increased risk of side effects.

How our drug bioavailability enhancers work

Our Insoluble Drug Delivery (IDD®) platform comprises a number of major enabling technologies to address solubility issues. The IDD® technologies use microparticles, microdroplets and phospholipids or other surface modifiers to support improved solubility. All excipients used are approved by the US FDA.

Soctec™ is a versatile gastroretentive technology designed to retain a drug in the stomach for an extended period of time so that it can be delivered in a controlled way to the duodenum and jejunum for subsequent absorption, so improving oral bioavailability and duration of action for sustained release formulations.

We also has a medicated chewing gum that can be used to improve bioavailability by solubilisation in saliva prior to swallowing.

Benefits of our drug bioavailability technologies

Our drug bioavailability technologies allow solid oral products to be developed as alternatives to intravenous or ophthalmic formulations of drugs that are currently only available in less desirable forms. The technologies offer the following potential benefits:

  • improved oral bioavailability;
  • formulations with lower toxicity;
  • rapid onset of action;
  • suitability for high drug payloads;
  • sustained-release depot formulations;
  • suitability across various dosage forms, including oral, topical and pulmonary; and
  • applicability to all therapeutic classes, for example anaesthetics, anti-cancer agents and immune suppressants.

Products incorporating the technology

Our IDD® technology is currently available in Triglide® that is marketed in the US.

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Soctec

Soctec is a versatile extended release gastro-retentive platform technology that has been designed to overcome many of the limitations of alternative systems.

Why is gastroretention important?

The oral route of administration is preferred for the majority of drugs, owing to its flexibility, ease of administration and patient compliance. However, many drugs are preferentially absorbed in the upper gastrointestinal tract. In order to target this "absorption window" it is often desirable to retain the drug delivery system in the stomach for an extended period of time so that the drug can be released slowly and so be absorbed more efficiently in the upper intestine.

How Soctec™ works

Soctec is an easy to swallow elongated capsule. It has an integral buoyancy chamber and a counter-balanced denser ballast to ensure that it floats upright in the stomach fluids as soon as it is swallowed.

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Normally the contents of the stomach are crushed by peristaltic contractions and the contents are rapidly expelled through the pylorus into the duodenum. However, owing to its shape and physical properties Soctec could be retained in the stomach for more than nine hours. During this time Soctec releases its drug load at a predetermined rate, allowing absorption in the small intestine's upper segments.

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Applications for Soctec™

Soctec can be used with a range of drugs that have a narrow absorption window and are preferably absorbed in the upper intestine segments. It can also improve the bioavailability of drugs that are degraded by the alkaline pH of the lower gastrointestinal tract. It is also suitable for drugs that are targeted for local action in the stomach and small intestine.

Benefits of Soctec™

Soctec is easy to swallow, allowing it to quickly enter the stomach where it starts to deliver its drug load. As a result of its in-built buoyancy and its elongated shape it could be retained in the stomach for more than nine hours, providing an extended period for drug release without disturbing normal food transit. Soctec is very adaptable and can be used with drugs having different physicochemical and therapeutic characteristics. The drug release profile can be tailored to the drug’s absorption characteristics and the clinical need. Soctec utilises conventional manufacturing techniques facilitating rapid and cost-effective industrialisation.

Medicated chewing gum

Skyepharma’s medicated chewing gum is suitable for either local delivery of drugs through the buccal mucosa or for use where systemic delivery can be improved by the active drug being solubilised in saliva prior to swallowing.

How our medicated chewing gum works

Our proprietary medicated chewing gum technology uses an approach similar to multilayer tableting. A combination of layers modulates the release rate of the active ingredients and flavouring agents when the gum is chewed. The active drug is released into the salvia for either local or systemic effect.

Benefits of our medicated chewing gum technology

Our medicated chewing gum is patient friendly and offers a convenient and discreet drug delivery solution. It is especially suitable for:

  • delivery of drugs that are metabolised by the gut wall or the liver, so avoiding the first pass effect whereby drugs are metabolised prior to entering the systemic circulation. This allows more rapid delivery and better bioavailability of the drug and therefore the use of lower doses;
  • bioavailability enhancement for poorly soluble drugs by facilitating their solubilisation in saliva before swallowing;
  • local buccal treatment by prolonging contact between the drug and the highly vascularised oral mucosa.