Newsletter LabialfarmaNewsletter n˚5 | December 2011

Leading participation at the CPhI 2011 in Frankfurt, the world’s largest international pharmaceutical exhibition!

With this newsletter we are proud to inform you about our successfully participation at CPHI.

LiqFillcaps International™, increases year by year its international presence playing a pioneering role with regard to the technology and process management needed for contract manufacturing and is well-positioned for future growth.

More about SELFCaps™…Comparative Study of the plasma concentration profile of celecoxib in healthy volunteers, after administration of a SMEDDS formulation with a conventional capsule.

SELFCaps™

LiqFillCaps Internacional™

ARONIA Concentrated in a fruit the greatest Antioxidant Power!

Aronia:Aronia melanorcarpa, is also called “Chokeberry”, for its fruit’s astringency which are inedible when raw.

RapidTabs™RapidTabs™ are fast disintegration tablets. Have the ability to quickly disintegrate and to dissolve in the stomach, right after the oral intake.

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What are RapidTabs™?

RapidTabs™ are fast disintegration² tablets¹. Have the ability to quickly disintegrate and to dissolve in the stomach, right after the oral intake.

¹ By definition, fast disintegration tablets have a disintegration time below 1 min.

² Disintegration is the first physical process that occurs in a tablet after being in contact with organic fluids or water.

• Quick relief of the symptoms• Faster absorption• Faster disintegration in the stomach

What are the main advantages of RapidTabs™?

• Can be dissolved in a glass of water (ideal for people who have difficulty swallowing solid dosage forms)• They disintegrate in water in less than 1 minute.

What are the benefits of RapidTabs™?

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Taking of the RapidTabs™

Rapid disintegration in the stomach

Rapid dissolution

Rapid absorption of the active

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Foodstuffs or ingredients for food, for which no data exists of significant consumption in the EU before May 15, 1997 are considered "novel foods" or "novel foods ingredients." All "novel foods" and "novel foods ingredients" must be submitted for Commission approval prior to marketing.

Did you know that...

Food supplements can contain a very diverse range of nutrients and other ingredients, including vitamins, minerals, amino acids, essential fatty acids, fiber and various plants and herbal extracts.

In the legislation is only defined the use of vitamins and minerals, in accordance with Regulation (EC) No. 1170/2009, and ingredients barely used in the European Union before May 15, 1997, considered Novel Food, in accordance with Regulation (EC) No. 1882/2003.

The LiqFillCaps™ SELFCaps™ formulations

Lipidic-based oral formulations are particular systems used for water-insoluble drugs in cases where typical pharmaceutical formulation approaches do not provide the required bioavailability, or when the drug itself is oil.

Recent developments in various methodologies employed to characterize resulting LiqFillCaps™ SELFCaps™ formulation system, such as globule size and shape, ability to encapsulate the drug, gastrointestinal and thermodynamic stability, rheological characteristics, and so forth, are vastly and comprehensively presented in the scientific literature and assist as a guide to LiqFillCaps™ in formulating an effective and robust LiqFillCaps™ SELFCaps™ formulation ready to be filled into a hard gelatin/hypromellose capsule or a soft gelatin capsule.

In a very suitable way, the LiqFillCaps™ SELFCaps™ formulations are described as lipidic-based oral formulations assigned either as Types II, IIIA or IIIB.

The LiqFillCaps™ SELFCaps™ formulation displays an incomparable potential in improving rate and extent of the absorption of poorly water-soluble drugs.

Immediately after oral administration, a LiqFillCaps™ SELFCaps™ formulation rapidly disperse in gastro intestinal fluids, yielding fine emulsions, micro- or nanoemulsions, designated as SEDDS (Self Emulsifying Drug delivery System), SMEDDS (Self-Microemulsifying Drug delivery System) or SNEDDS (Self-Nanoemulsifying Drug delivery System), respectively, all containing the solubilized drug.

A remarkable advantage of LiqFillCaps™ SELFCaps™ formulation is the direct result of its miniscule globule size and composition, thus the micro/nanoemulsifed drug can easily be absorbed through lymphatic pathways, bypassing the hepatic first-pass effect.

¹Pouton, CW, 1999. Key issues when formulating with lipids. Bull. Tech. Gattefosse 92, 41 – 50.

²Subramanian, N, et al., 2004. Formulation design of self-emulsifying drug delivery systems for improved oral bioavailability of celecoxib. Biol. Pharm. Bull. 27(12), 1993 – 1999.

Plasma Concentration Profiles of Clecoxib in Healthy Adults after Oral Administration of Optimized SMEDDS ( ) and Conventional Capsule ( )

These particular cases of formulations are conventionally classified according to the system originally described by Pouton¹. This system describes four classes of lipidic-based formulations, namely Types I, II, IIIA and IIIB, according to the concentrations of triglycerides or mixed glycerides, surfactants, hydrophilic cosolvents, particle size of the dispersion, significance of aqueous dilution, and significance of digestibility.

As an illustration of the great importance of LiqFillCaps™ SELFCaps™ formulation, an example is taken from the scientific literature . Here, the plasma profiles of celecoxib in human volunteers after administration of an oral conventional formulation (Celecoxib 200 mg) and SELFCaps™ hard gelatin capsule containing a SMEDDS formulation (Celecoxib 200 mg) were compared. Pharmacokinetic parameters, including the AUC0 - Infinite, the maximum plasma concentration (Cmax) and its corresponding time (Tmax) of the SMEDDS formulation were significantly different from the conventional capsule (p <0.05). The values of AUC0 - Infinite and Cmax derived from the SMEDDS formulation increase of 1.32 and 1.21 times and the Tmax decreased by 2 times compared to conventional formulation. The relative bioavailability between the conventional and the SMEDDS formulations was 132 %.

In simplistic way, a LiqFillCaps™ SELFCaps™ formulation comprises the drug solubilized in a mixture of oil, surfactant(s) and/or co-solvents. The LiqFillCaps™ SELFCaps™ formulation results in faster drug release from emulsions, micro- or nanoemulsions in a reproducible manner, which can be designed further to make the release characteristics independent of the gastro intestinal physiology and the fed/fasted state of the patient.

The results indicate that the SMEDDS formulation increases the speed and rate of absorption of the drug considerably.The improved bioavailability of the drug is due to increased solubility and the rapid and efficient dispersion of the drug in the gastrointestinal tract.

BASIC REQUIREMENTS FOR GOOD MANUFACTURING PRACTICE:

Logbooks for cleaning and calibration of equipment;

Standard procedures covering all aspects of manufacturing;

Control of the manufacturing environment, air and water;

Identification of all materials and testing of raw materials, labels and packaging;

In the case of plants, identification must be confirmed by comparison with a reference material to verify that each part and plant species are correct;

Traceability (batch identification, batch records);

Reconciliation (raw materials, products, packaging and labels);

Procedures for release;

Stability tests of the finished products;

Procedures and records of complaints;

In the case of plants, microbiological tests and trace contaminants such as pesticides, heavy metals and radioactivity.

Analysis;

Validation of equipment and processes;

The fundamental requirements for Good Manufacturing Practice (GMP) for herbal products are common to apply to medicinal products.Procedures and Best Practices under the observances include:

Herbal Health Products: Good Manufacturing Practice from raw material to the finished product

Unlike conventional pharmaceutical products (medicines) which are usually prepared from synthetic materials through techniques and reproducible manufacturing processes, the herbal products are prepared from plant materials, materials that can be subjected to contamination and deterioration, and may vary in composition and properties.

The control of raw materials, storage and processing are phases that have particular importance due to the complex and variable nature of many herbal products and the small number and amount of active ingredients that are presently well-defined.

Thus, the manufacturing process is one of the main steps of monitoring to ensure the quality of the final product. The application of GMP ("Good Manufacturing Practices") in the manufacture of Herbal health products is an essential tool to ensure their quality.

Moreover, in the manufacture and quality control of herbal products, procedures and techniques that are used are often substantially different from those used for conventional products.

Quality is, in the terminology of ISO 9000, the degree of satisfaction of requirements - needs or expectations expressed by the customer - for a given set of intrinsic characteristics of a particular product or service, which is perceived by the customer, meeting it’s needs or even exceed his expectations.

According to Edward Deming, organizations can, by adopting appropriate principles of management, increase the quality of goods and services by increasing customer loyalty, while reducing costs by reducing waste, decreasing the repetition tasks and the reduction of conflict and labor disputes.

Thus, Deming proposed a Quality Model for organizations:

Deming also stated that "the conversation about the quality doesn’t do anything by itself. Action is needed and we must not forget that the consumer is the most important part of the production line thus the quality should focus on customer needs and in the future." This is why it is necessary to give special attention to customers whose needs must be identified, satisfied and even exceeded, to ensure their loyalty.

This is achieved if organizations work effectively. For this purpose, they need to determine and manage numerous linked activities. An activity or set of activities using resources, and managed to enable the transformation of inputs into outputs, can be considered as a process, and is identifying the various processes, together with the interactions between them and their management - Process Management - which will allow:

On November 10th, the World Quality Day was celebrated. Increasingly, organizations are aware of the importance that quality has on their growth and prosperity. QUALITY is a value essential to achieving sustainable development and Excellence. It is for this reason that all elements of the organization must understand the importance of quality and contribute daily to the fulfillment of customer and legal requirements, sharing ideas and methodologies that can contribute to the continuous improvement of the organization.

Quality can have several meanings:

Can be synonymous of Excellence in a transcendental approach;

Collection of products or services free of errors, if we consider an approach based on production;

Collection of products or services whose measurable characteristics meet the requirements necessary to satisfy the consumer, if the approach is based on the product;

The perceived quality as a function of relative value (utility) / price if the approach is based on price.

Collection of products or services appropriate to their purpose, if the approach is based on use;

Improvement of Quality

Increase of Productivity

Costs Reduction

Price Reduction

Increase of the market

Business Continuation

More jobs and better business recuperation

Understand and fill the requirements and customer expectations;

Consider processes in terms of added value;

Get results of the performance and effectiveness of the process;

Continuously improve processes based on measurement of objectives.

The Quality and Quality Management Systems

The implementation of a Quality Management System should not be faced only as a customer requirement, but primarily as a subsystem for the overall management strategy of the organization.

Generally, a Quality Management System is a set of interrelated elements and inter-acting to implement the Policy and Quality Objectives, and to achieve these objectives.

The Quality Management Systems are starting points for structurated organizations, serve as the base for other management aspects, that according to the specific needs of each organization, which are developing at the rate of the business.

As a gear interdependent systems management must work in concert rather than counter-current.

The future will undoubtedly pass by a robust Quality System and must support and actively contribute to the sustainable development...

An organization should establish a Quality Management System with three basic objectives:

establish a systematic approach of the problems (since R&D, to manufacture and post-market);

focus on preventive measures rather than relying only on the results of monitoring and inspection;

provide objective evidence that the quality was achieved.

This can only be achieved through the implementation of Quality Management Systems, supported the principles of Quality.

The Quality and Quality Management Systems

Results Driven

Costumer Focus

Leadership and constancy of purposePartnerships Development

Development and involvement of people

Management by processes and facts

Continuous learning, improvement and innovation

Corporate Social Responsibility

ARONIA – Concentrated in a fruit the greatest Antioxidant Power

Aronia, Aronia melanorcarpa, is also called “Chokeberry”, for its fruit’s astringency which are inedible when raw.

What is Aronia?

We must put a sachet in a cup with boiling water and let steep for 5 to 10 minutes, preferably covered.

How do I prepare this Aronia infusion?

Aronia presents the greatest ORAC (“Oxygen Radical Absorbance Capacity”) value.

The ORAC Absorption Capacity or Oxygen Radical is a laboratory test that defines the potential power of an antioxidant food. Aronia presents the highest antioxidant potency, ie, the greatest ability to neutralize free radical aggressors of our body.

Why Aronia is so interessing?

Aronia melanocarpa (black chokeberry) has attracted scientific interest due to its deep purple, almost black pigmentation that arises from dense contents of phenolic phytochemicals, especially anthocyanins – a powerful antioxidant.

What are Aronia’s main constituents?

The fruit infusion is a natural source of vitamins A, C, B1, B2, B6, E, K, P, PP, minerals and other trace elements.

O que podemos encontrar nas bagas de Arónia?

Drink herbal and fruit teas enriches our daily diet with necessary components for the proper functioning of the body. With a fantastic flavor and aroma, these infusions can replace any of your conventional teas (black tea) in our diet as a refreshing drink and tasty.

Why driking Aronia Tea?

Aronia Infusion is presented in individuals sachets, in two different formulations.

How is the Aronia infusion presented?

ARONIA BERRIES - CH02295

ARONIA WITH FRUITS COMPLEX - CH02296

You must try them!

Are you interested?Contact:

WELLCARE Tel. 231 927 590 Fax. 231 929 165email@wellcare.pt

The focus of our presence was based on the following topics:

International Expansion

Full-service PROVIDER in the pharmaceutical and food supplement fields

Technological innovations: galenic and packaging solutions (SELFCAPS™ and blister DUO)

VIGIA: Liqfillcaps’ unique pharmasurveillance interactive program

LiqFillCaps International™ – leading participation at the CPhI 2011 in Frankfurt, the world’s largest international pharmaceutical exhibition

With this newsletter we are proud to inform you about our successfully participation at CPHI.

LiqFillcaps International™ has made available to its customers and visitors a more complete pharmaceutical and nutraceutical service.

Alongside the existing services, we have offered an enhanced portfolio of finished products, based on customer’s requirements and new clinical supported actives.

Our innovating blister DUO and the Picasso bottle exclusively developed by us, allow our customers to launch into the market the most effective pharmaceutical forms with the most convenient actives in the most therapy compliance packagings.

LiqFillcaps International™, increases year by year its international presence playing a pioneering role with regard to the technology and process management needed for contract manufacturing and is well-positioned for future growth.

In this sense, and in order to be closer to our customers, we have informed our visitors about the opening of our new commercial office in Barcelona-Spain.

Operating since 2008 in Portugal, the VIGIA System arose from the need to develop strategies to strengthen the safety of food supplements, raising the level of consumer protection.

Unique in the world, the VIGIA System consists in detection, assessment, management and prevention of events not related to the function of the product.

The VIGIA System offers to its users, a team of experts consisting in physicians and pharmacists - the VIGIA Team. Whenever, after taking a food supplement integrated in VIGIA System, an event, not related to product’s function occurs or is suspected, or if there is

Laboratório de Produtos Farmacêuticos e Nutracêuticos S.A.Edifício Labialfarma Nº1 - Felgueira3450-336 Sobral - MRT - Portugal

Telef. +351 231927590 | Fax: +351 231929165

www.labialfarma.com

Edition: Aída Lacasa – Pharma MScCatarina Madanêlo - Pharma MScCláudia Barroso – Pharma D SpecialistCristina Godinho - Pharma DHelton Santos - PhD, Pharmaceutical TechnologyInês Gonçalves - Pharma MScPedro Laranjo - BiologistTeresa Telo - Pharma D Specialist, MBA

Rui Cruz - BiologistRevision:

The LABIALFARMA welcomes your comments

Contact us for more information or send us your suggestions.

VIGIA SYSTEM IN SPAIN!

any doubt about interactions or posology, the VIGIA Team should be contacted as soon as possible.

Recently, the Vigia system extended its scope and is already operating in Spain.

900838131vigia@labialfarma.comwww.vigia.labialfarma.com

Spain Contacts:

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