Pharmaceutical Deformulation / Reverse Engineering of a Product’s Formulation

                         

                        

Pharmaceutical Deformulation / Reverse Engineering of a Product’s Formulation

 

Step 5: Formulation and process development… Cont….

 https://pharmatutor21.blogspot.com/2021/02/generic-product-development-key-steps-l_7.html

Understanding of RLD product:

 Understanding of information available in ‘Label’ section

The PIL/Label will provide the information regarding the qualitative composition of the formulation. In this case qualitative formulation of Table and Oral Solution. Let us explore the Tablet formulation.

              Step-1:

             From the PIL, we can get the information

             1.     Strength: abacavir sulfate equivalent to 300 mg of abacavir

2.     Active pharmaceutical ingredient: Abacavir [available as a salt form]

3.     Inactive ingredients: (i) Microcrystalline cellulose (MCC), (ii) Sodium starch glycolate (SSG), (iii) Colloidal silicon dioxide and (iv) Magnesium stearate

4.     Coating composition: hydroxypropyl methylcellulose, polysorbate 80, synthetic yellow iron oxide, titanium dioxide, and triacetin

Step-2:

·       From step -1, one can only get the quantitative information of the API i.e 300 mg of          Abacavir. 

·      From the RLD product or during physical characterization of the RLD table, one can take the weight of the table. The weight of the table including the contribution of coating materials.

Based on the above information, some one is having the total table weight and weight of the API. Therefore, the remaining weight [Tablet total weight - (coating weight + API)] is the contribution from the active ingredients i.e. (i) Microcrystalline cellulose (MCC), (ii) Sodium starch glycolate (SSG), (iii) Colloidal silicon dioxide and (iv) Magnesium stearate.

How to get the quantitative information for these inactive ingredients and even how to understand the API characteristics. In this scenario, Pharmaceutical deformulation, the reverse engineering of a product’s formulation plays a vital role.

Pharmaceutical Deformulation, the reverse engineering of a product’s formulation, is a necessary process to create generic drugs. Even before patent expiration, skilled chemists must perform a detailed analysis to identify, quantify, and characterize the original formula’s active pharmaceutical ingredients (APIs) and its excipients, whether it’s a drug or supplement.

Successful generics companies are the first to market after patent expiration, bringing bioequivalent products to pharmacies as quickly as possible. They achieve this through having solid reverse engineering programs and by utilizing outside labs when necessary to help in the process.

 What is Pharmaceutical Deformulation?

Deformulation is the analysis of a product where a lab breaks down a material or product to determine the identity and quantity of its components. Sometimes known as “chemical reverse engineering,” this process enables scientists to take a medication and discover the contents of its core and coatings. This is the method necessary to create a generic version of a medication and requires various chemical processes to discover the exact contents of a formula.

Why Do Generics Companies Need to Reverse Engineer Medications?

Just because a medication’s patents expire doesn’t mean the original patent holders have to divulge the formulas. For a generics company to obtain approval under ANDA (Abbreviated New Drug Application), it must demonstrate a bioequivalent product. The blood levels of the active ingredient must be highly similar in the generic composition to the original product. The FDA, however, considers the innovator’s formula proprietary, and won’t give it out to any generics company. Proper characterization of the API ( particle size, polymorphic form, solubility etc) and the excipients grade plays a vital for successful bioequivalent study outcome.

 

How Does Reverse Engineering Work?

Pharmaceutical deformulation can be a complex process and will differ depending on the composition of the drug in question. The first step begins with 1st level deformulation, which identifies and quantifies the major ingredients. In this step, quantitation is not performed. This level of analysis is only used to verify label claims and assist a chemist with the formulation. 2nd and 3rd level deformulation quantitate the components of the formulation, including coating systems and agents used to mask the taste, and will ensure the ANDA is approved by the FDA quickly.

Once you’ve decoded the quantitative formula, the components need to be separated and individually quantified using gravimetric or other detection tools, like UV light. It’s important that the new generic formula uses the same polymorphic form as the RLD (Reference Listed Drug) to ensure similar stability and dissolution profile, as well as to pass the ANDA. After someone have got the formula down, it’s necessary to decide on a manufacturing method, such as wet or dry granulation, direct compression, or other methods, based on the properties of the drug.

Understanding the role/use of each inactive ingredient in the formulation is very important. The inactive ingredient information can be obtained from ‘Handbook of Pharmaceutical Excipients’.