Excipients Community

"Excipients are a very diverse set of materials and simple descriptions are simply not detailed enough to capture their complexity. For example, "lactose" can exist both as anhydrous and hydrate crystals, it can vary considerably in its compaction properties depending on how it is processed and vary in its anomeric content. In order to specify the required characteristic of the excipients used in any given formulation, excipient descriptions need to include much more information than the chemical composition or common name that is used in standard reference texts. It is not unreasonable to suggest that some type of systematic classification or naming system--"taxonomy"--is required to specify exactly what excipients are to be used in any given formulation. Case studies will be presented to better recognize basic taxonomy approaches with an eye toward the excipient landscape and understand the gaps in current excipient classification and nomenclature"

Hi Folks, 

As stated in the above about excipient and their various aspect of not only from use bout what is the intention of the product development formulator to use them for what purpose in a particu;ar formulation may not be understandable to a CMC reviewer not having Pharmaceutics background or experience of product formulation. In my career as the product development scientist over a period of more than 35 years I have used the same common name excipient e.g. lactose, MCC, HPC and many others for my desired function I wanted it to provide in the particular formulation.   

.Let me share below a few of such cases of using excipient specifically from Pharmaceutics perspective.

1. In a formulation of solid dosage for a tablet with very low drug load less than 1.0% I have used a small quantity of Anhydrous Lactose as a career for its rugged surface making an initial Premix concentrate for the API. !:1 API and Lactose Anhydrous by sandwiching the API between two layer of lactose anhydrous. Thus, the small quantity of the API now attached with the rugged surface of the lactose anhydrous, would not easily separate. Thus helping ultimate BU and CU characteristic of the ultimate final blend and drug product respectively. Now for a dry blend direct compression final blend there was a need for the blended materials' good flow property. Hence, in the rest of the blend lactose anhydrous cannot be used for its poor flow. So I have used in the next step Lactose Monohydrate Fast Flo with MCC grade Avicel PH102 by ordered mixing.  

2. In this example the purpose of using Lactose Anhydrous and Low moisture MCC (Avicel PH112)  were used to compensate loss of mass in a needed a Stoichiometric reaction between API and KHCO₃

The intention of the formulator of using such excipients is explained below:

Making Enalapril Maleate tablets had the following formulation Challenges;

·         Like most of the "Prils" cyclization to form DKP degradation

·         Hydrolysed to form "Prilate"

Problem:

Addition of KHCO₃ resulting effervescence reaction. Loss of mass due to liberation of CO₂.

Solutions

–        Stoichiometric reaction between API and KHCO₃ in a liquid environment and adding resulting solution to the substrate for wet-granulation

EM + KHCO₃ ® EK + KM + CO_2­ + H₂O

–        Use of Lactose Anhydrous

–        Use of low moisture MCC [PH112]

–        ( to compensate loss of mass)

Hope you folks will now understand why a formulator uses some excipients not for its bare knowledge of its general use purpose. In the above two cases the lactose anhydrous was used for in case 1. as a DS career for BU CU purpose and in the second case the lactose anhydrous along with low moisture microcrystalline cellulose PH112 were used in an wet granulation system to hydrate thus helping to compensate loss of mass happened due to a effervescent reaction happened using potassium bicarbonate for the stability of the drug. This type of use of the excipients by the formulator is his away of thinking and applying specially in PIV type of ANDA.

Thanks

Masih Jaigirdar