Micro-Sphere - Liquid and Dry Micro-Encapsulated Formulation Contract Development

Micro-Sphere was founded in 1998 and started its activity in 2000 in the factory in Madonna del Piano (Switzerland). Micro-Sphere has the ISO 9001:2000 certification and operates under cGMP conditions. The company is regularly inspected by Swiss authorities (Swissmedic) and by its customers.

The main services offered by Micro-Sphere are:

• Formulation development
• Preparation of samples for clinical studies
• Nano-technology (nano-emulsions, nano-particles)
• Micro-encapsulation
• Spray drying (organic solvents, inhalation)
• Analytical services

Micro-Sphere's clean-rooms are operating in class D (100'000). To avoid powder cross-contamination of the production rooms the air-conditioning system uses 100% fresh air.

Water for solutions is prepared by reverse osmosis and subsequently treated by electro-deionization. The quality of water is according to USP purified water (aqua purificata) specifications. On request water can be supplied as 'highly purified water' according to the European Pharmacopoeia. Compressed air and nitrogen are also of pharmaceutical grade.

FORMULATION DEVELOPMENT

Micro-Sphere is active in proposing to customers the development of formulations either on already known products or ex-novo development in order to deliver a new proprietary formulation. Lipid-based formulations are a key knowledge of the company.

MICRO-ENCAPSULATION

Micro-Sphere offers the technology of fluid bed using the Hüttlin machines, recently updated by Disk Jet technology. A laboratory scale machine Hüttlin Unilab-5-DJ is used to develop new or modified generic formulations in the field of micro-encapsulation (enteric coating, pH dependent release, extended release).

The scale-up to the pilot machine is performed on Hüttlin HKC-50-DJ with a batch size up to 45kg, an optimal quantity for clinical trials or small productions. In case of molecules which are sensitive to oxygen or if the presence of organic solvents is necessary, the machines can be operated under nitrogen.

SPRAY DRYING

Micro-Sphere offers also the technology of spray-drying having installed a Niro Mobile Minor 2000. The spray dryer can be used either with compressed air or by nitrogen. Spray drying is one of emerging technology in formulating active substances with particular interest in field of pulmonary delivery (particle size <5µm).

A further application of actual interest is the formulation of molecules with poor bioavailability in lipid-based systems. Liposomes or emulsions are prepared by the technique of high pressure homogenisation reaching dimensions in the nanometer range (100nm - 800nm). Subsequently, the solutions can be dried in the spray dryer as inert carriers.

LACTO-SPHERE® LACTOSE FOR INHALATION

Micro-Sphere's know-how is particularly aimed at the development of inhalation products with pulmonary and systemic action:

• Choice of the best particle size and morphology for active ingredients and carriers
• Optimisation of dry powder formulation of different active ingredients tailored for customer's inhalers

Lacto-Sphere® is lactose for inhalation specifically developed by Micro-Sphere as a carrier for Dry Powder Inhaler (DPI) formulations.

Lacto-Sphere® meets the requirements of the United States Pharmacopoeia / National Formulary, the European Pharmacopoeia and the Japanese Pharmacopoeia monographs for lactose monohydrate.

Key benefits of Lacto-Sphere® are:

• Sourced from BSE-free country (USA)
• Non-rennet
• Production under cGMP conditions
• Customisable

Available documentation:

• DMF
• MSDS
• Certificate of origin
• Statement of compliance with the 'Note of guidance on minimising the risk of transmitting animal spongiform encephalopathy agents' (EMEA/410/01/Rev.2)
• Statement of compliance with the EC Decision on 'Laying down rules for the prevention, control and eradication of certain transmissible spongiform encephalopathies' (EC 999/2001)
• Statement of absence of GMO material in the final product

Lacto-Sphere® is manufactured under controlled environmental conditions. The particle size distribution is routinely determined by laser diffraction. The narrow particle size distribution confers to Lacto-Sphere® unique, remarkable characteristics, essential for a full performing lactose for inhalation.

Lacto-Sphere® is offered in three different particle-size distributions:

• Lacto-Sphere® MM3 (micronized) - X50 - 2µm - 4µm
• Lacto-Sphere® MM50 (sieved) - X50 - 40µm - 60µm
• Lacto-Sphere® MM250 (sieved) - X50 - 220µm - 280µm