IBSA is engaged in the development of innovative technologies, new formulations and drug administration and delivery systems that are more functional to treatment, as well as more targeted at people’s needs. These technologies represent the quality and the excellence of IBSA’s scientific research.
The Assisted Reproductive Technology (ART) area is an important challenge for the pharmaceutical sector, and for this reason IBSA patented exclusive extraction and purification processes, and implemented plants dedicated to the production of fertility hormones (gonadotropins), starting from the urine of pregnant and menopausal donors.
The range of fertility hormones is produced in compliance with the highest standards of purity, efficacy and safety, while preserving the structure of glycoproteins. In fact, the processes patented by IBSA combine advanced technologies with a full knowledge of the relationship between the structure and function of gonadotropins, thus making them a quality benchmark. The gonadotropin production process follows several phases: collection of postmenopausal and pregnancy urine, a few purification steps and, finally, the filling process.
Thanks to research and development, IBSA has marketed the only progesterone formulation in aqueous solution that can be administered subcutaneously. The new water-soluble formulation of progesterone, patented by IBSA, improves compliance. Once injected and absorbed, the progesterone molecule immediately dissociates from the complex formed with hydroxypropyl-β-cyclodextrin, remaining free in the bloodstream, as if the hormone had been physiologically produced by the corpus luteum.
The polyolefin plastic vial is a well-known form of primary packaging, and is frequently used for the administration of liquid products for single use (typically in the ophthalmological area). IBSA’s intuition was to exploit this administration system in order to ensure the release of precise doses of drug for oral use, dissolved into a defined volume. The use of the single-dose vial is particularly suitable for formulations based on thyroid hormones, because it allows to provide the patient with the exact dose, ready for use in the dosages prescribed by the specialist, while avoiding the excessive use of preservatives, indispensable in multi-dose formulation.
PEARLtec technology is a process for creating softgels (soft capsules) that allows a liquid matrix, in suspension or gel, to be incorporated within a continuous shell of soft gelatine. Once weighed, the capsule components are processed in a special device called turbo-emulsifier, where the perfectly balanced excipients are mixed together and prepared for the next phase. The core of the process is the encapsulation phase (PEARLtec): an extremely accurate syringe-pump injects the previously formulated active ingredient into a mass called filler, inside the capsule being formed. In this way, very small transparent pearls are formed, consisting of two shells heat-welded together.
Through in-process checks, all essential and critical parameters are verified and therefore the quality of the finished product is kept under control; in addition, before being packaged, the capsules are visually inspected one by one, to eliminate all imperfections. This technology allows a liquid solution to be taken in solid form, and is particularly suitable for formulations with very low concentrations, because it ensures uniformity and precision of dosage.
Hyaluronic acid (HA) – a molecule naturally produced by the human body – concentrates in the derma and the synovial fluid.
It performs important functions, including lubricating and protecting the articular cartilages and moisturising the skin and mucous membranes. The abundance of hyaluronic acid physiologically reduces with age, or in the presence of certain diseases, for example joint diseases. For this reason, in some situations it becomes very useful to restore an adequate concentration of HA in the tissues, by means of injections – viscosupplementation – of hyaluronic acid.
IBSA has developed and patented the Nahyco® Hybrid Technology, which allows to deliver high dosages of hyaluronic acid, optimising the viscous and elastic properties of the formulation and improving its resistance to degradation. With this technology, polymer chains of different lengths (i.e. of different molecular weight) are used: through a thermal process, and without the use of cross-linking chemical agents, high molecular weight and low molecular weight hyaluronic acid (H-HA and L-HA, respectively) give rise to hybrid cooperative complexes. In this way, high concentrations of HA can be reached without compromising the ease and safety of injection, and effectively mimicking the physical and mechanical properties of a healthy synovial fluid, thus optimising the concept of viscosupplementation. The same Nahyco technology can also be successfully used in other indications, such as to restore the physiological content of HA in the skin, improving the water content – and therefore the appearance – of the aging derma. Also in this case, the Nahyco® technology allows to easily deliver high dosage of HA, which are distributed in the derma for an optimal result, and to ensure maximum safety, thanks to the use of high purity hyaluronic acid which – having been obtained by fermentation and not by extraction from animals – is identical to that present in the human body, and devoid of any chemical modification. The Nahyco® technology is mainly applied to hyaluronic acid, but can also be extended to mixtures of high molecular weight hyaluronic acid with other polymers of the same family (glycosaminoglycans or GAGs, to which chondroitin also belongs). In this way, the hybrid cooperative complex can be formed, for example, by combining high-weight HA and biotechnological sodium chondroitin, where the latter – obtained by IBSA by fermentation through a patented process – plays a similar role to that of low molecular weight hyaluronic acid.
IBSA has the technological know-how to develop and manufacture medicated patches, both single- and multi-layer, designed to act locally or systemically, depending on the site of action of the active ingredient. Both types, produced thanks to Hydrogel and Drug-in-adhesive technologies, are protected by a patent, and this know-how makes IBSA unique in the pharmaceutical landscape, as one of the few companies in the world capable of offering both. The structure of these patches is normally composed of an adhesive matrix – in polyacrylate, silicone or other adhesive – containing the active ingredient, a backing layer and a protective layer, which is removed before application; in more complex cases, the structure can include multiple layers of adhesive containing different concentrations of active ingredient. The patch for topical use can be formulated to have a local action in a limited area only (eg. diclofenac and piroxicam), or a transdermal, systemic action (eg. nitro-glycerine and fentanyl). This device can deliver a drug in a controlled manner, for periods of time ranging from a few hours to a week, offering many advantages over oral administration, including maintaining optimal drug concentrations, reducing the frequency of administration and increasing tolerability.
Finally, compared to the oral route, the use of the patch avoids the hepatic first-pass effect, and allows to optimise bioavailability and to reduce undesirable effects. The field of application ranges from patches with anti-inflammatory activity to patches with dermatological activity. The extensive technological know-how and its production capacity make IBSA one of the world’s largest producers of topical patches; the company has also innovated these technologies, registering numerous patents.
In order to overcome some limitations of the traditional packaging and to have a more versatile solution, suitable for different products, IBSA has introduced in its plants the Bag on Valve (BoV) packaging technology. In this type of packaging the product, both solid and liquid, is placed in a protective bag, consisting of a laminated and heat-sealed multilayer film (aluminium and plastic). This bag, on top of which is a dispensing valve, is contained in an aluminium cylinder. The system is completed by a dispensing button which, when pressed, activates the valve and releases the product contained in the bag. BoV packaging provides several advantages over traditional packaging, tube or spray with propellant:
Also called “oral” films, orodispersible films are a new oral dosage form, the characteristics of which can improve treatment adherence in people with needs which are not met by capsules and tablets. They are small, thin, flexible, postage stamp-like sheets that dissolve quickly on contact with saliva. Thanks to the water-soluble filming polymer of which it is composed and to the added plasticiser, an orodispersible film is resistant to traction, elastic and flexible, properties that ensure a good handling – very important for the user – and adequate workability, essential for large-scale production. IBSA has selected maltodextrin as the main polymer, bringing to an industrial scale a patented formulation platform that is the basis of IBSA’s FilmTec technology. Maltodextrin has the advantage of being a common food ingredient, inexpensive, of good palatability, with rapid dissolution times in the mouth and a neutral taste. Orodispersible films always allow an immediate release: the film releases its components very quickly and can therefore facilitate and speed up their absorption compared to a tablet or a capsule. In some specific cases, depending on the nature of the active ingredient, orodispersible films can also improve the absorption of active and functional ingredients. Orodispersible films are user-friendly, and for some populations – such as subjects with dysphagia, bedridden people, elderly and children – their use in place of traditional oral forms becomes a necessity, rather than a simple preference, because it allows a precise and accurate dosage even for those who have difficulty swallowing or cannot use water to facilitate the intake.
The use of syringe-vials – i.e. syringes pre-filled with the right volume of product – greatly simplifies the administration of sterile injectable products and reduces the risk of errors, thus improving safety. The formation of bubbles in the syringe and the risk of contamination, which are always possible when withdrawing from ampoules, vials or bottles, are excluded. The pre-filled syringe-vial ensures the administration of a definite dosage – with complete recovery of the product – as well as sterility. IBSA can manufacture sterile pre-filled syringe-vials of different capacities, formats and materials. The availability of highly automated lines allows to achieve high production volumes, while the predominant use of glass syringes, combined with a rigorous control of the interactions of the product with the packaging, allows to ensure the quality and stability of drugs and injectable medical devices. Among the pre-filled syringes is the intra-bladder glycosaminoglycan (GAG). Developed by IBSA, the product consists of 50 mL Crystal Clear pre-filled syringes (1.6% HA, 2% CS, 0.87% CaCl2) and a new patented medical device (IALUADAPTER®) which allows to inject a solution of glycosaminoglycan into the bladder through a minimally invasive procedure, that does not require a catheter. IALUADAPTER® can be an alternative to the use of standard male and female catheters, and its main advantage is that it eliminates the pain associated with catheterisation. With IALUADAPTER®, the solution passes directly into the bladder via the urethra, and simultaneously treats both the urethral and bladder mucosa.
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