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Phospholipid-Based Delivery Systems: Injectable Depot Formulations

Because many drugs have a short biological half-life, multiple administrations are needed to achieve a therapeutic effect. In addition, drugs may not be suitable for oral administration because of degradation in the gastrointestinal tract and poor absorption. These include high molecular weight proteins and peptides. For such drugs, extended-release depot injectables for local or systemic applications enable a more patient-friendly, low frequency therapy, leading to a better compliance.

Extended drug release can be achieved by various formulation strategies. For intermediate release periods (days up to several weeks), lipid-based and especially phospholipid-based formulations are an interesting and innovative depot-injectable approach (Fig. 1).

Fig. 1: Overview of categories of phospholipid-based depot technologies: (A) drug suspension, (B) multivesicular liposomes, (C) in situ formed depots at injection site.

Compared to polymer depots, phospholipid depots exhibit favorable degradation profiles related to the formation of less acidic products. All this together makes phospholipids highly interesting excipients for depot injectables.

Phospholipids are nowadays successfully used in numerous approved and marketed depot formulations and are being investigated in ongoing research and development projects using various technologies.

Lipoid offers a wide range of large-scale available natural and synthetic phospholipids of pharmaceutical quality to formulate innovative depot injectables with optimized drug release profiles.

„Good Morning Meeting“ in Copenhagen

At the „Good Morning Meeting“ in Copenhagen

Lipoid presented on natural and synthetic phospholipids for innovative drug delivery systems, covering vaccines, pulmonary applications and depot formulations. Thanks a lot to all attendees, the exceptional interest in our materials – cGMP phospholipids for your products from R&D to commercialization – and the fruitful discussions.

Participation in the 18th „Annual Skin Forum 2022“ in Malmö – we would be pleased to meet with you

The Skin Forum brings together internationally recognised experts from all over the world to advance skin research through knowledge and information exchange.

Each year, the Skin Forum organises an annual meeting with distinguished keynote speakers as well as students, clinicians, scientists and industrial stakeholders to present and discuss the latest research outcomes and regulatory developments.

Lipoid is official sponsor of the 13th „Global DDF Summit“ – visit us at booth # 21

The „13th Drug Delivery and Formulation Summit“ is all about showcasing the most exciting and innovative developments in pharmaceutical technology.

The 2022 Summit covers small molecules and biologics, new technologies, concepts and case studies in areas such as:

• Formulation design for poorly soluble compounds

• The potential of nanotechnology for better deliverability

• The latest controlled released technologies

• and many more

Lipoid at Vitafoods Europe 2022 in Geneva – the Nutrition and Health Market’s Top Venue

Lipoid was one of more than 1,200 exhibitors participating in this world-leading event for food ingredients, actives and raw materials, dietary supplements and services, which was attended by around 25,000 nutrition industry experts.
Bringing together all stakeholders in a constantly evolving dietary-supplement sector, this year’s show took place in Halls 2, 4, 5, and 6 of Geneva’s Palexpo Exhibition and Congress Center on May 10 to 12, 2022, and was a resounding success.

Longstanding contacts could be revived and intensified and many new contacts forged. Moreover, the concept of offering not only natural raw materials but also ready-to-use systems was seen to be fully justified.
In particular, our carrier systems attracted considerable interest because they facilitate fast and straightforward product development. Liquid formulations containing fat-soluble active ingredients such as coenzyme Q10, curcumin, or omega-3 fatty acids, as well as liposomal vitamin C, are available for direct bottling, obviating any need for additional manufacturing steps.

Our preformulated liposomes or phospholipid-vegetable oil mixtures have proved to be extremely popular for developing individual solutions. They constitute versatile carriers for a wide range of active ingredients introduced into formulations simply by stirring.

Whether preloaded systems or products of in-house development – our phospholipids excel by virtue of their natural characteristics and provide enhanced oral bioavailability without any need for synthetically produced additives.

Phospholipid-Based Delivery Systems: Advanced Vaccines in Modern Medicine

Vaccine Adjuvants

The routine use of vaccines is one of the most outstanding accomplishments of modern medicine. The first major milestone was the eradication of smallpox. Nowadays, emerging pathogens like Sars-CoV-2 require innovative vaccination approaches. Besides the prevention of infectious diseases, vaccination is also an emerging field to prevent and treat cancer.

The first generations of vaccines were made by use of live attenuated organisms or inactivated organisms, followed by specific antigens and most recently by antigen encoding mRNA. Antigens often induce only a low immune response. In such cases, adjuvants are needed to boost and/or modulate the immune response. Adjuvants can be classified into carrier systems and immunostimulants or antigens.

Carrier Systems

Carrier systems include e.g. oil-based emulsions, Immune Stimulating Complexes (ISCOMs), liposomes, lipoplexes and lipid nanoparticles (LNPs). Natural and synthetic phospholipids, mainly phosphatidylcholine, often called “lecithin” in American literature, and other phospholipids relevant for the adjuvant use are often explored and attract more and more attention (Fig. 1).

Such systems are used as carriers for immunostimulants, antigens or mRNA along with cationic lipids like DOTAP for complexation (Fig. 2). In addition, certain phospholipids of the carrier systems like DOPC and DOPE play a major role in intracellular processing. Since the advent of COVID-19 vaccines based on LNPs and mRNA, wherein phospholipids are essential components, the interest in lipid carriers is tremendously increased.

Immunostimulants

In 1925, Ramon demonstrated for the first time in horses that artificial enhancement of diphtheria and tetanus antitoxin levels by the addition of immunostimulants like agar, metallic salts and saponins is possible. In the 1940s, first trials were performed with water-in-oil emulsions as adjuvants. These so-called Freund adjuvants comprised mineral oil emulsions. Freund adjuvants are no longer used in marketed vaccines as they are poorly tolerated due to the nondegradable mineral oils present. Nevertheless the use of aluminium salts is well established, immunostimulants like saponins, Monophosphoryl Lipid A (MPL).

“Lipoid goes Rotterdam” – Gold Sponsor on the 13th PBP Meeting

Between March 28th and 31st Lipoid welcomed its customers and friends at their booth on the 13th PBP World Meeting in Rotterdam. This conference series is continuously gaining in impact among the pharmaceutical scientists: With close to 1000 submitted abstracts and more than 1300 participants it has become a well-established major meeting, attracting scientists from all over the world.

Importantly, the entire spectrum of topics in the fields of Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology will be covered. This includes for example engineering aspects of manufacturing processes, the portfolio of commercially available excipients enabling formulation of a large variety of drug products and medical devices, the underlying basic sciences (e.g., physico-chemical principles), cutting-edge characterization techniques of dosage forms in vitro and in vivo, as well as potential pitfalls and hurdles to be overcome during product development, manufacturing and quality control.

Phospholipid-Based Delivery Systems – Advanced Pulmonary Applications Using Phospholipids

Phospholipids in Pulmonary Formulations

Phospholipids, in particular saturated phospholipids like dipalmitoylphosphatidylcholine (DPPC), are the main components of lung surfactant. As endogenous molecules they provide unique advantages for pharmaceutical formulations. They are biocompatible, biodegradable, and recognized as safe for pulmonary drug delivery [1].

The administration of phospholipids to the lungs has proven successful for decades in the treatment of pathological conditions characterized by a lack of phospholipids in the lung tissue, especially in the alveoli, as in the case of respiratory distress syndrome (RDS) [2]. Pulmonary drug delivery is the preferred route of administration for the local treatment of respiratory disorders such as respiratory distress syndrome, asthma, and chronic obstructive pulmonary disease (COPD).

It is also gaining interest for the systemic delivery of low molecular weight compounds, peptides, and potentially proteins, as it allows fast absorption, low metabolism rates and avoids invasive administration routes [3]. Phospholipids are further used as technical excipients, acting as solubilizer or dispersant, for stable drug formulations. They may serve as structure-giving agents and to improve the physical characteristics of drug delivery systems. Moreover, phospholipids can modulate the pharmacokinetics of a drug by enabling a sustained drug release or enhancing the drug permeability through the lung epithelium [4,5].

Phospholipids are flexible excipients: depending on the headgroup and the fatty acid composition, they harbor different characteristics such as phase transition temperature, size, and polarity. Chemical modifications, e.g. pegylation, further expand their versatility. The selection of a distinct lipid composition enables the generation of formulations with applicationoptimized specific properties.

The Lipoid Group Expands Capacity at Its Cologne Facility

Groundbreaking Ceremony at Cologne on January 19, 2022

The Ludwigshafen-based Lipoid enterprise, which supplies excipients to the global pharmaceutical industry and operates four independent production facilities in Germany, remains on a continuous growth track. A medium-term investment in the triple-digit million-Euro range is currently underway at the company’s Cologne site, PHOSPHOLIPID GmbH, to construct a modern production and laboratory complex, a pharmaceutical warehouse, and a new steam generation and cooling water unit, all on a total area in excess of 15,000 m2.

Implementation of this project is in the hands of a 20-person interdisciplinary team covering the areas of engineering, quality assurance, quality control, production, and procurement, which is working together with local architects, specialist planners, and other experts.

The impact of the COVID pandemic and resulting changes in working conditions during the planning phases led to cancellation of face-to-face meetings. However, preparatory measures could be completed in less than 12 months following approval of the early start of construction in March 2021. This allowed the symbolic groundbreaking ceremony to take place as early as January 2022 – with participation of local politicians, representatives from the immediate neighborhood, as well as the project team.

Commissioning of the plants for steam and cooling water generation will follow in the course of this year. Completion of the warehouse building is already planned for the first quarter of 2024. The areas for quality control, quality assurance, as well as administration should be ready to move in by the end of 2024 at the latest. Commissioning of the production building is likewise scheduled for the fourth quarter of 2024.

Through implementation of the planned process and plant engineering, the corporate group intends to substantially enhance the capacity of this site while simultaneously complying with its self-imposed sustainability goals.

According to the overall project manager Dr. Lorenz Gabel, these investment projects are based on a clear decision of the Lipoid Group to pursue long-term development of the existing site.

 

Fig. 1: 1. to 3. Pharmaceutical warehouse and laboratory complex, 4. Steam generation and cooling water plant, 5. Production building

Topical Applications – Formulate Dermal Pharmaceutical Products with Phospholipids

Phospholipids are the excipients of choice in dermal formulations to modulate the interaction of active pharmaceutical ingredients (APIs) with the skin.
Phospholipids have unique multifunctional properties. They are natural components of every human cell. Therefore they are highly biocompatible and well tolerated – even by sensitive skin. The external application of phospholipids makes it possible to influence the degree of skin interaction: On using natural unsaturated phospholipids fluidization of the stratum corneum allows the penetration of APIs into deeper skin layers, while use of saturated (hydrogenated) phospholipids will restore/improve the barrier function of the skin in order to keep APIs in place longer [1].

In addition, they can replace missing or attenuated substances in the stressed skin (e.g. linoleic acid) via instrinsic metabolic pathways in the skin. Besides their use as penetration enhancer or retention time prolonger, phospholipids can also act as emulsifiers, natural moisturizers, texturizers or emollients, highlighting their role as multifunctional excipients contributing multiple benefits to dermal formulations [2].

Two classes of phospholipids (saturated phospholipids and unsaturated phospholipids) and three classes of phospholipid-based delivery systems (liposomes, emulsions, and lamellar structures) are commonly used in dermal pharmaceutical products. Saturated (hydrogenated) phospholipids have a phase transition temperature above the skin temperature and therefore form rigid structures that enhance the skin retention time of actives, while natural unsaturated phospholipids have a phase transition temperature below the skin temperature, enabling the formation of more flexible carrier systems with increased skin interaction, resulting in deeper tissue penetration of active ingredients [3].
In addition to being used to functionally improve dermal drug products, phospholipids can also be considered to make pharmaceutical form line extensions, by replacing other functional excipients [4,5,6].