EPIGRAPH

Method for encoding pharmaceutical solid forms with an authentication code, a bulk powder encoding device and a product certification process.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to the codification of pharmaceutical products, more precisely solid pharmaceutical forms, by means of an authentication code to certificate and verify the authenticity and the origin of these products in a traceability process. In particular the present invention relates to a method for codification of solid pharmaceutical forms, the solid pharmaceutical forms thus codified and a device for encoding such codified solid pharmaceutical forms. The present invention also relates to the process of certification and verification of the authenticity and the origin of codified solid pharmaceutical forms and the detection of counterfeit or imitated or falsified or adulterated products, along the supply chain of such products.

2. Background of the Invention

The certification of authenticity of pharmaceutical dosage forms and other health products along the supply chain has been an urgent task to combat counterfeiting and to control geographic distribution of these products, from manufacture to acquisition by the consumers. The certification of authenticity is substantial to guarantee the consumers safety and is necessary to take measures to improve the control of counterfeiting and create a traceability method to follow the geographic distribution of such products.

In the case of pharmaceutical counterfeit or falsified products, it may include the original pharmaceutical products, branded ones or generic ones. In some cases the counterfeiters copy or imitate the drug, in other cases the drug may not have the active pharmaceutical ingredient or may own a harmful or improper product.

This is a serious worrying problem because the counterfeit products have already penetrated in the health systems of countries like United Kingdom and United States of America, creating harmful effects on patient's health and survival. Counterfeiting occurs both with branded and generic products. It has been found that counterfeiters copy or imitate existing products but they also manufacture products that are completely invented. Also, the pharmaceutical product certification is a critical issue at pharmacovigilance. When serious cases of adverse side effects occurs in patients taking some type of pharmaceutical therapy, it isn't possible to known if the adverse side effects are due to the proper medicine or due to a counterfeiting product.

The consumer's security is a priority and is the focus of pharmaceutical and commercial norms and regulations. However, counterfeit products have also negative economic impact. Counterfeit products are commercialized in a parallel market without paying fiscal taxes. In 2010 the market value of all counterfeit drugs in circulation exceeded 75 billion dollars or 15% of the global market. They represent losses for the pharmaceuticals companies, which lose up to 30 billion dollars annually. Globally, in 2007, life sciences industry lost 90 billion in revenue due to counterfeit drugs. The impact includes sales lost to the "grey market" and to parallel trading; increased cost of goods sold and reduced returns on huge investments in development.

The crescent need in regulation against counterfeit medicines has led to the development of an entire industry providing technological traceability and product certification solutions for these products. Processes and engines for product identification, against falsification, adulteration or imitation already exist. The traditional anti-counterfeiting procedures require the localization of the original packaging using radio frequency tags (RFID), barcodes, watermarks, fluorescent dyes or biological/chemical markers (Dei Singh, Analyst 2005; 130: 271-279). Nevertheless some of these techniques such as barcodes or watermarks can be easily counterfeit (Deisingh, Analyst 2005; 130: 271 -279). Besides the high efficiency of these methods, they cannot prevent at the distributer or at any step of the supply chain, the fraudulent repacking of pharmaceutical product, replacing the original product in its original pack for counterfeit product. An authentic packaging doesn't necessarily correspond to authentic contents. The traceability systems (e.g. track and trace) include both hardware (identification tags, printers and scanners) and software components (ePedigree, serialization and track-and- trace). The RFID technology prevail over the barcodes due to its advantage in speed, range and storage capacity, as well as its unique ability to scan multiple items at once from any orientation. All of these technologies are paper-based and dependent of product's package quality level. They assure the traceability of the package but not of the product itself. They don't protect against sophisticated repacking of counterfeit product in certified packaging.

3. Description of the related background of invention

Several of the anti-counterfeiting measures currently adopted by pharmaceutical manufacturers involve package tracking. To track a packaging, radio frequency tags, barcodes, watermarks, fluorescent inks, and chemical and biological tags are used (Deisingh, Analyst 2005; 130: 271 -279). Radio frequency identification is fast and easy to use (Deisingh, Analyst 2005; 130: 271-279). Barcodes and watermarks may be detected by a simple digital scanner, and therefore they can be easily counterfeited (Deisingh, Analyst 2005; 130: 271-279). Furthermore, such methods are only effective if the repackaging of the drugs does not occur at any step of the supply chain, thus confirming that authentic packages are not sufficient to verify the authenticity of the content. Tags directly applied to the pharmaceutical drug, combined with package labeling, would increase the efficacy of anti -counterfeit methods.

Some examples of inventions that track or verify the authenticity of products packaging are well known. Some of them are here described:

The invention 2007/016374 A2 (WILDEY, C et al) (08.02.2007) is an apparatus and method for security tag detection, that uses luminescence properties from different compounds to print diverse optical signatures in security tags at the packaging, avoiding counterfeit products.

Several other methods can prove the authenticity of a pharmaceutical drug by applying standard analytical techniques. Examples of such methods are:

- Liquid chromatography coupled with mass spectroscopy;

- Capillary gas chromatography; - Thin layer chromatography;

- Ultraviolet-visible spectroscopy;

- Nuclear magnetic resonance spectroscopy (1 H, I3C, 15N); or

- Diffusion-ordered two-dimensional nuclear magnetic resonance spectroscopy.

However, these techniques require sample preparation and they may be destructive and time consuming. Nevertheless, there are other techniques that do not destruct the pharmaceutical sample and are fast methods to detect counterfeit pharmaceutical forms:

- Raman spectroscopy;

- Infrared spectroscopy.

One example of a Raman spectroscopy is described in the publication US 2012/0300201 A1 (OWEN, H. et al) (29/11/2012) which is an example of a method that uses a combined near-infrared laser source two-dimensional array collecting anti-Stokes Raman spectra and a probe configured to produce a larger spot on the sample for analysis. This enables to measure low concentrations of critical components, including low-dosage, high- potency pharmaceutical samples.

The NIR techniques may be used to determine the homogeneity of a batch and to screen for the presence of the active pharmaceutical ingredients (API) despite standard analytical methods still being necessary for definitive confirmation.

The present invention comprises an infrared spectroscopy analysis, although the method here disclosed is not limited to screen the presence or the absence of the API. The present invention allows for the screening of codified pharmaceutical forms, through a method of codification wherein small amounts of codification markers were added during the manufacturing process of the pharmaceutical forms, aiming to produce a unique and unambiguous spectrum that will function as a product signature.

Some practical examples of inventions that track or verify the authenticity of products will be described:

The US patent application 2007/0219916A1 (LUCAS, M.) discloses a system to print alphanumeric codes in pharmaceutical products in order to identify their origin in the pharmaceutical supply chain. The US patent application 2007/0160814A1 (MERCOLINO, T. J.) describes a method to identify coated tablets by a signature array, through the incorporation of a great number of different substances in the coating film of tablets. The US patent application 2013/084249 A1 (LAWANDY; Nabil M.) presents authenticate coatings for pharmaceutical tablets and ingestible materials by using spherical particles stacked in the coating film of tablets. The coatings are formed from a lattice of particles stacked to cause selective diffraction, creating an optical signature. Then the signature is associated to each coating that can be read and authenticated.

Other techniques aiming to track drugs without destroying that product are known. Some use invisible marks printed in a tablet that can be detected by X-ray diffraction, and then allow to identify genuine products, as the disclosed patent application PCT/US2012/042443 (WARD, M.) (20.12.2012).

Other solutions for drug authentication consider the variation of the inactive ingredients of solid pharmaceutical forms. Then through a near-infrared spectroscopy is identified the genuineness of products. The US publication 2007/086625 A1 (POLLI, J. E. et al) is an example of that, because it varies the relative percentage of one or more inactive ingredients of a formulation, and then is possible to verify the modifications in near- infrared spectra. However, this invention changes the products unit weight, so it means that the pharmaceutical forms will differ its weight from batch to batch and this can be a limitation for a standardized method for labeling pharmaceutical products. Moreover, the number of possible variations of inactive ingredients will be limited, being difficult to avoid repetitions. On the other hand, the process for the variation of inactive ingredients is also a critical factor for mass production of drugs during its industrial manufacture, because not all inactive ingredients can be significantly altered. For example, in the cases where microcrystalline cellulose is used as an excipient, a great variation of this inactive ingredient is required in order to create a substantial impact on the infrared spectrum. However, small variations in the inactive ingredient that are present at low concentration in the product formulation can also be critical for the manufacturing process and do not cause substantial impact on the infrared spectrum. Thus, a great need for an adequate invention that assures the authentication of such pharmaceutical forms still exists. The invention here disclosed presents a high level of security, quick and easy application to products, guarantee of authentication, difficult to adulterate and reply, automated, simple to be used by the consumers in the industry and legally accepted by regulatory authorities. The present invention overcomes the already known solutions: keeping unchanged and not destroying the original formula of the product; not causing manufacturing problems during the addition of the small amounts of the codification markers used to produce endless and distinctive infrared spectra; allowing codification of solid pharmaceutical forms without infringement of manufacturing process and the quality of the final product.

The invention solves the mentioned problems through a method for codification of solid pharmaceutical forms with an exclusive and unequivocal authenticity code, a bulk powder encoding device and a process of certification. Besides, it keeps the unit weight of the pharmaceutical form constant and does not affect the validation of the industrial manufacturing process

Throughout the description and claims the word "comprising" and variations thereof, do not exclude other technical characteristics, compounds or steps. Other objectives, advantages or characteristics of the invention will become clear for experts in the field after the analysis of the description or performing the invention. The examples and drawings are presented as a way of illustration and do not intend to limit the invention.

SUMMARY OF THE INVENTION

The present invention comprises spectral analysis, more precisely infrared spectroscopy (IR), to detect specific spectral variances in IR spectrum obtained from solid pharmaceutical forms, and creating a code which functions as a product signature. Those spectral variances are obtained after adding small amounts of codification markers to the pharmaceutical powders mixture, they function like a code which produce modifications in the product infrared spectra which allows the authentication of solid pharmaceutical forms throughout the supply chain until the end user.

The method for codification of solid pharmaceutical forms comprises some steps. It requires the addition of different combinations of small amounts of codification markers, particularly pharmaceutical grade markers, to the pharmaceutical mixture of powders during the manufacture process. The final mixture will correspond to the pharmaceutical product to be codified and to be authenticated. The combinations and ranges of concentration of the codification powder markers to be adding to the final mixture will generate a unique infrared spectrum detectable through infrared spectroscopy device. The association of that spectrum to a set of manufacturing data, such as batch number, manufacture date and location or expiration date, will allow identifying any solid pharmaceutical form manufactured by this method, such as tablets, capsules or powders in sachets.

Throughout the industrial manufacture process it is usual that solid pharmaceutical forms require a step for the mixture of pharmaceutical powders. The present invention is applied during that step, adding the codification markers in different combinations and ranges of concentration during the mixture of the pharmaceutical powders, and according to the method for codification described in the present invention it allows the creation of an exclusive spectrum, ensuring the uniqueness and the certification of a solid pharmaceutical product.

The method for the codification of solid pharmaceutical forms requires a bulk powder encoding device. This bulk powder encoding device is responsible to add to the powder mixture small and accurate amounts of pharmaceutical-grade powder markers. For the creation of an exclusive IR spectrum for the pharmaceutical products being produced, the amounts of each powder marker must differ between which one for every pharmaceutical form being produced.

For the achievement of a final spectrum capable to ensure a product signature is required an iterative process between the spectrum obtained with the addition of the codification markers and read by the IR probes, installed on the walls of the industrial powders mixture and the existent spectra stored in data base. Then to confirm its exclusivity the spectrum is compared with the spectra stored on a database. If the spectrum is unique over that database (or a set of database libraries), the spectrum is stored in the database associated to the combination and the amounts of each codification marker added to that particularly powder mixture and API dosage. Moreover that specific spectrum is also associated in that data base with the manufacturing information of that product such as: batch number, manufacture date, manufacture location, expiration date, dosage of pharmaceutically active ingredient (API), brand and other details. So, this method for codification requires determining the combination of markers and ranges of concentration of one, or more, codification markers to be applied on a solid pharmaceutical form, which may not be present in the original recipe of the pharmaceutical product. The combination of markers and the concentration ranges of the codified markers must make at least one intense and distinct spectrum band in infrared spectra. This is crucial to confirm if the infrared spectrum is exclusive and unequivocal for that product. If the result of the infrared spectrum is not exclusive or unequivocal for that product the process is repeated and a new addition with other amounts/concentrations of the codification markers is performed, until an exclusive and unequivocal infrared spectrum is in fact obtained.

Once obtained an exclusive and unequivocal infrared spectrum for the pharmaceutical form being codified, the process of manufacture of solid pharmaceutical form continues. This codification is made by a bulk powder encoding device suited into an industrial powder blender. This device is required for the accurate addition of codification powder markers into the pharmaceutical mixture of powders blended during the manufacturing. Moreover, the present invention allows the possibility to associate a set of manufacturing information, such as batch number, manufacture date, manufacture location, expiration date, dosage of pharmaceutically active ingredient (API), brand and other details, to the infrared spectrum. Thus is possible to ensure the authenticity and the origin of the codified pharmaceutical form through a process of certification and verification that requires the infrared reading spectrum of the product, preferentially a Fourier transform infrared spectroscopy (FT-NIR) device.

BRIEF DESCRIPTION OF THE DRAWINGS The examples and drawings presented here are ways of illustration and do not intend to limit the method for encoding solid pharmaceutical forms with an authentication code, a bulk powder encoding device and a product certification process.

An exemplary embodiment of the present invention is illustrated by means of an example in the accompanying drawings, in which the preferential example is based on 6 (six) depots for the codification markers, wherein an infinite number of combinations is produced in order to obtain exclusive and unequivocal infrared spectra.

Figure 1 is a diagrammatic representation of a cross section of a depot (1 ), from a bulk powder encoding device. The codification marker (3) is stored inside the depot of the bulk powder encoding device (2). The depot (1 ) has an opening (4) to introduce the codification marker, and integrates the bulk powder encoding excipient device assembled in the cover of an industrial powder blender (5). A wireless controller (6) connected to a database via radio frequency is represented here, from where it receives data containing information about combinations of amounts of codification markers to be added to the industrial bulk powder blend. The controller also transmits back to the database the data related to the infrared spectra obtained from the pharmaceutical mixture of powders manufactured after the addition of codification markers. The addition of the codification marker (3) to the powders mixture blended (7) inside the industrial powder mixture (8), is made by an accurate dosing system (9) connected with the dispenser (10) responsible for introducing the accurate amount of codification markers to the powder mixture blended.

Figure 2 is a diagrammatic representation of side perspective view of a bulk powder encoding device suited over the cover of an industrial powder blender. A wireless controller (6) receives

data via radio frequency, containing information about combinations of amounts of codification markers to be added to the pharmaceutical form being produced. The infrared probes (7) are installed on the walls of the industrial powders blender, in order to gather spectral information from the pharmaceutical powders blend.

Figure 3 is a diagrammatic exploded perspective from the top of preferred embodiment of the bulk powder encoding excipient over the cover of an industrial powder blender. The industrial powder blender is used to blend the excipients and the active pharmaceutical drugs during the manufacturing process of solid pharmaceutical forms. In the cover (5) a bulk encoded device with a plurality of depots is represented on the top of the industrial powder blender, wherein this preferred embodiment six depots (1) are used to store the codification powder markers; openings (11 ) for recharging and dosing codification powder markers to the inside of the industrial powder blender; an orifice for the dispenser tube (12) wherein the codification marker is added inside the industrial powder blender; a dispenser (10) for the accurate addition of codification markers to the blended mixture inside the industrial powder blender; a wireless controller (6) that receives data from the database, containing information about combinations of amounts of codification markers to be added to the industrial bulk powder blend, and also transmits back to the database, the data related to the infrared spectra obtained from the pharmaceutical mixture of powders manufactured after the addition of codification markers. Figure 4 is a diagrammatic exploded perspective of the bulk powder encoding device, suited over the cover of an industrial powder blender. Figure 5 is the spectrum obtained for Diffuse Reflectance Infrared Fourier transform spectroscopy (DRIFTS) of a commercial premix of excipients ready to produce a solid pharmaceutical form Prosolv EasyTab® (PS), with 3 different amounts and combinations of pharmaceutical-grade markers (AM9, AM10 and AM11 ). Medium infrared spectral region between 4000-400 cm ^"1 , with spectra normalization at 2900 cm ^"1 which is the unique band due to the Prosolv EasyTab® excipient mixture. These spectra shows that tree different combinations (AM9, AM10 and AM11 ) of two codification powder markers produce distinct spectra for the same powder mixture which is, in this case, the commercial premix of excipients Prosolv EasyTab®. Figure 6 is the spectrum obtained for Diffuse Reflectance Infrared Fourier transform spectroscopy (DRIFTS) of commercial premix of excipients Prosolv EasyTab® (PS), with 3 (three) different amounts and combinations of pharmaceutical-grade markers (AM9, AM10 and AM1 1 ) using an amplification of the region between 1800-850 cm ^"1 , with spectra normalization at -1045 cm ^-1 .

DETAILED DESCRIPTION OF THE INVENTION

The following terms used in the disclosure of the present invention have the following meanings:

"Pharmaceutical product" is a solid pharmaceutical form, considering a dosage form that comprises one or more active pharmaceutical ingredient (API) - biologic, synthetic or nutraceutical - and one or more inactive ingredients, in particular pharmaceutical excipients.

"Pharmaceutical form" is any group of pharmaceutical substances whose aim is to deliver one or more than one API, by any way of administration, such as in the form of tablets, hard capsules or powders sachets.

"Pharmaceutical-grade marker" considers an excipient communally used in the pharmaceutical industry and in the case of the present invention is able to cause a modification of the infrared spectrum of the pharmaceutical form being codified. "Excipient" is a regulatory approved pharmaceutical substance, or composition of substances, without pharmacological activity and suitable to be including in the pharmaceutical dosage form.

"Counterfeit" denotes a product that has been mislabeled or otherwise adulterated with respect to identify and/or source. A product manufactured by an unapproved source is counterfeit.

"Counterfeit pharmaceutical product" or "counterfeit product" are terms indicating faked, adulterated or mislabeled medicines or products from the real/original product. It can be also a manufactured and/or commercialized product without the supervision and authorization of Regulatory authorities, and which do not comprise properly the therapeutic API.

"Product signature" is infrared spectrum of a pharmaceutical product after the addition of different amounts and combinations of codification markers, in order to obtain an exclusive and unequivocal infrared spectrum.

The present invention discloses a method for codification of solid pharmaceutical forms comprising the follow steps:

- Determining the combination and ranges of concentration of one or more than one codification markers to be applied on a solid pharmaceutical form, for obtaining at least one intense spectral band of the said codification markers in infrared spectra distinct from the components of the solid pharmaceutical form, in order to create an unique spectrum for that product, which will be stored in a database;

- Adding one, or more than one, codification markers, blended according to specific ranges of concentration, which correspond to available codes of codification, in order to obtain an unique infrared spectrum signature for the product to be codified;

- Determining the exclusivity and intensity of the obtained infrared spectral band comparing the infrared spectrum after the addition of the codification markers to the pharmaceutical mixture of powders and the infrared spectra already stored in a database;

- If the obtained infrared spectral band is not exclusive and unequivocal, repeat the steps mentioned before, readjusting the ranges of concentration of the codifications markers, to be added to the mixture inside the industrial powder blender until ensure the exclusive and unequivocal infrared spectrum for the product being codified;

- Associating the exclusive and unequivocal infrared spectrum, obtained for the solid pharmaceutical form being codified to a set of manufacturing data such as batch number, manufacture date, manufacture location, expiration date, dosage of pharmaceutically active ingredient (API), brand and other details, and storing it in a database;

- Using the exclusive and unequivocal infrared spectrum of the solid pharmaceutical form as the product signature, associating said signature with the manufacturing data mentioned in step e), and storing it in a database.

The databases used are information systems that store and manage information, namely the association between the obtained spectrum and respective manufacturing product data. The databases are crucial to guarantee the process of certification and verification of the authenticity of the pharmaceutical forms along the whole supply chain by comparing the spectra obtained from the product with the respective manufacturing information existing in the database.

The aim of the disclosed method is obtaining an exclusive and unequivocal spectrum from the pharmaceutical solid form as a product signature used in the authentication process for a pharmaceutical form along the supply chain from the manufacturing to the commercialization of such products.

The pharmaceutical forms correspond to a mixture of one or more than one API and excipients. The API are all compounds that are classified as such by the Regulatory Authorities, and that can be used with excipients on the formulation of solid pharmaceutical forms such as tablets, capsules or powder in sachets. In a preferential embodiment of the invention, Prosolv EasyTab® is a commercial premix of excipients that represents a typical industrial mixture of excipients.

The codification markers are excipients suitable to be included in the pharmaceutical dosage forms, more precisely solid pharmaceutical forms.

The method for the production of a codified solid pharmaceutical form (tablets, hard capsules or powders in sachets) also considers a step consisting in the association of the obtained infrared spectrum with a set of information related manufacturing data. Then the data is stored in a database. The codification markers employed for the present invention may be selected between every pharmaceutical-grade compound that produces, isolated or in combination, an infrared spectral band distinct from the original pharmaceutical form. In a preferred approach of the invention the codification markers are selected among pharmaceutical-grade pigments, isolated or in combination. Some pharmaceutical-grade pigments that may embody the present invention are erythrosine and/or tartrazine. However other dye pigments may be applied. The concentration of the codification markers should be lower than 1.0%, preferentially between 0.1 % and 1.0% of the weight of the solid pharmaceutical form, and more preferentially between 0.2% and 1.0% of the weight of the solid pharmaceutical form. This represents a minimal percentage weight variation in the final formulation and does not change or influence the manufacturing process of the pharmaceutical form, whether it is a tablet, a hard capsule or a powder in sachets.

To obtain the infrared spectra is used a spectroscopy reading device, more precisely a diffuse reflectance infrared Fourier transform (DRIFT), that is capable to obtain the infrared product signature from a powder mixture. The present invention discloses an obtained codified pharmaceutical form, based on the method for codification described before.

Additionally, the present invention discloses a bulk powder encoding device, for coding solid pharmaceutical forms, which is suited to an industrial powder blender. This bulk powder encoding device comprises the following features:

- A plurality of external depots to store the codification powder markers suited radially on the top of the industrial powder blender, containing openings for recharging and dosing control devices for the addition of codification powder markers, to the inside of the industrial powder blender;

- A plurality of dispensers for codification markers, each one containing a worm gear, for the accurate addition of codification powder markers inside of the industrial blender, and according to the codification codes designated by a database;

- A plurality of dosing tubes which accommodates inside an accurate powder dosing system. This system contacts, at one end, with the codification markers, and in the opposite end with the interior of the industrial powder blender; - A wireless controller that receives radio frequency data from the database, containing information about combinations of amounts and combinations of codification markers to be added to the industrial bulk powder blend, and also transmits back to the database, the data related to the infrared spectra obtained from the pharmaceutical mixture of powders manufactured after the addition of codification markers. It commands the introduction of codification markers, according to the data received from the database;

- Infrared probes to gather spectral information from the pharmaceutical powders blend after the addition of codification markers, and send that data to the wireless controller.

The number of external depots, dispensers and dosing tubes vary according the number of different codification markers desired to introduce. Using only two codification markers is already sufficient to produce a number of combinations and spectra modifications, sufficient to codify a pharmaceutical product, as it is disclosed in the examples of the invention. However, a preferred configuration of the bulk powder encoding device comprises six external depots, dispensers and dosing tubes, in order to apply six different codification markers. For this process any conventional industrial power blender available in the market can be used for the manufacturing process of pharmaceutical forms, for blending the excipients and the API.

The present invention, instead of presenting a method of certification for packaging, labels, signatures, watermarks or other extrinsic/superficial marks of pharmaceutical products, it considers process of certification for the own pharmaceutical forms. It takes advantages on the fact that small amounts of codification markers added to the producing powder mixture produce a unique infrared spectrum, used to codifying pharmaceutical forms. Hence, the present invention is not an identification or reading process, but a method of codification based on the modifications produced on the infrared spectrum of a solid pharmaceutical form.

The presented invention discloses a unique and unambiguous process of certification and verification of the authenticity and origin of codified solid pharmaceutical forms, and without damaging the product. The process of certification and verification of the authenticity and origin comprises the follow steps:

- Providing a database to the manufacturers of pharmaceutical products comprising qualitative and quantitative information about qualitative and quantitative combinations of codification markers available to certain API, dosage and pharmaceutical form, in order to obtain a unique and unambiguous IR spectrum for the product being codified;

- Codifying mixtures of powders during the production of solid pharmaceutical forms with the addition of different amount combinations of more than one codification markers, in order to obtain a unique and unambiguous infrared spectrum, wherein consists in the product signature;

- Associating the manufacture and pharmaceutical product information to the infrared spectrum, and storing that data in a database;

- Providing that data in the database to the users of this invention along the pharmaceutical supply chain;

- Obtaining the infrared spectrum of the solid pharmaceutical form through a reading device, preferentially a Fourier transform infrared spectroscopy (DRIFT);

- Accessing the information on the database with the stored spectra, countersigning that the spectrum obtained from the solid pharmaceutical form is related with the manufacturing information, and is also in accordance with the information displayed on the product packaging;

- Certification of authenticity of the pharmaceutical form, if the information displayed about the spectrum is the same as the information indicated on the packaging. The present invention guarantees the traceability of the pharmaceutical form itself and not the packaging, even in case of repackaging. This improves the process of detecting counterfeit products, thus unmasking counterfeiting products placed inside certified packaging. In these cases the IR spectrum obtained from the pharmaceutical form does not match the information stored in a database.

Other than verifying and certifying of the authenticity and the origin of solid pharmaceutical forms, the proposed method differentiates from other existing methods by not requiring the preparation nor destruction of the pharmaceutical forms samples, neither requiring the application of subsequent analysis to confirm the results, a step required, for example, in standard analytical methods. Contrary to other existing, and already disclosed, solutions that need to vary the excipients quantities in order to authenticate a pharmaceutical form, the present invention comprises small additions of codification markers and proportional deductions on the excipients amount, thus maintaining the unitary weight of the pharmaceutical form. On preferred embodiment of the invention, the deduction is performed on the excipient presented in greater proportions, usually the diluent, for example microcrystalline cellulose. The codification markers are selected from any pharmaceutical-grade compounds that change the infrared spectrum, preferentially in regions of the spectrum distinct from other components that integrate the pharmaceutical form. The codification markers are preferably selected between pharmaceutical-grade dyes, as for example erythrosine or atrazine. They can also be used in either an isolated or combined way.

All information related to the manufacturing process is sent to the database or a library database via internet, and may be shared between different users of this invention along the supply chain (pharmaceutical property owners, producers, distributors, regulatory authorities, pharmacies).

EXAMPLES OF THE INVENTION The following examples serve to illustrate three applications of the invention, considering the use of two codification markers. However, these examples should not, in any way, be interpreted to limiting the broad of the invention.

Example 1 - Preparing a powder mixture designated as AM9

A powder mixture designated as AM9, with pharmaceutical-grade premix excipient, commercially available under the trademark Prosolv EasyTab® (PS) - JRS Pharma, Germany, in its original form, and ready to produce tablets by direct compression, with the pharma-grade markers Eritrozine (ER) and Tartrazine (TZ) as the codification markers. The powder mixtures were prepared by blending the Prosolv EasyTab® (PS) as an example of a typical pharmaceutical powder blend with pharmaceutical-grade markers ER and TZ. The AM9 mixture was prepared according to the following concentrations, in percentage by weight:

- PS: 99.6%;

- ER: 0.2%;

- TZ: 0.2%.

Then, KBr (Potassium bromide) was added to the mixture, in a 1 :4 proportion, for the resulting mix to be analyzed by Diffuse Reflectance Infrared Transform Spectroscopy (DRIFTS), in the spectral range used for the pure compounds.

The powder mixture AM9 was characterized by DRIFTS analysis, in medium infrared spectral region between (4000-400 cm-1 ), first by DRIFTS with spectra normalization at 2900 cm-1. Here, the unique/visible band was almost exclusively due to the Prosolv EasyTab® (PS) matrix. Then, the spectral region was amplified between 1800-850 cm-1 , with a spectra normalization at -1045 cm-1. The obtained analysis can be verified in Figure 5 and Figure 6, respectively. Example 2 - Preparing a powder mixture designated as AM10

The powder mixture designated as AM 10 was produced similarly to Example 1 of the invention. However, the amounts and concentrations of pharmaceutical-grade premix excipient, PS, and the pharmaceutical-grade markers, ER and TZ, were modified, according to the following concentrations, in percentage by weight:

- PS: 98.2%;

- ER: 0.9%;

- TZ: 0.9%.

The mixture was processed, and then the DRIFTS analysis was performed, in the same way and conditions as in Example 1. The obtained analysis can be verified in Figure 5 and Figure 6, respectively.

Example 3 - Preparing a powder mixture designated as AM11

The powder mixture designated as AM1 1 was produced similarly to Example 1 of the invention. However, the amounts and concentrations of pharmaceutical-grade excipient, PS, and the pharmaceutical-grade markers, ER and TZ, were modified, according to the following concentrations, in percentage by weight:

- PS: 99.1%;

- ER: 0.5%;

- TZ: 0.4%.

The mixture was processed, and then the DRIFTS analysis was performed, in the same way and conditions as in Example 1. The obtained analysis can be verified in Figure 5 and Figure 6, respectively.

The Figure 5 and Figure 6 represent graphs of the infrared spectra obtained for the three demonstrative mixtures aiming to illustrate the presented invention. It proves that different amounts of codification markers (ER and TZ) produce exclusive and unequivocal infrared spectrum in a typical pharmaceutical powder blend (PS) for which powder mixture exemplified (AM9, AM10 e AM11 ).

It verifies that the codification markers used, ER and TZ, present different spectral regions, with distinct maximum of absorption (respectively 1700-1300 cm-1 and 900-500 cm-1 ). The Prosolv EasyTab® presents wide spectrum bands. However, there are two regions, between -1650-1490 and -880-790 cm ^"1 , without matrix bands, where the vibrational modes of the employed codification markers can be observed. In Example 1 and Example 3 it is clear the existence of a spectral region that can be considered as a signature for each composition (the product signature), when the Prosolv EasyTab® was inferior to 99.6% and the codification markers were superior to 0.4% of the percentage by weight.

Hence the invention here disclosed is object of several variations and modifications, all of them within the scope of protection in the claims presented. Furthermore, all details or technical specificities can be replaced by other technically equivalent elements. An expert in the area understands that the present invention may be adapted to other suitable codification markers and other industrial powder blends without reconsidering the scope of the invention. In practice, the pharmaceutical compounds or pharmaceutical-grade markers and its amounts or concentrations can vary, according to each replication of the invention. When some technical characteristic was mentioned in a claim and referenced according to some amount or range amount, these should be interpreted as a way to increase the intelligibility of the claims, and do not should be interpreted as a limiting effect on the interpretation of the claim.