Generic pharmaceutical drug development A generic pharmaceutical drug is a drug that contains the same chemical composition as the drug which was protected by chemical patents. The generic drug product development’s main steps include characterization of the reference product, design of a bioequivalent product, and bioequivalent study. Let’s study the process in detail:
Before development
At first, the product which is to be developed is selected. To make a proper selection, the input is needed from a variety of disciplines such as:
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R and D Regulatory Affairs Legal Marketing and sales Finance etc. After selecting the right product, its details are recorded in a document that includes information like:
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Product Description and Dosage form product packaging Description Innovator product sales Generic product description Generic sales forecast Intended manufacturing site Other relevant information Based on the patent’s expiry, availability of ingredients, etc., the project is scheduled, and the progress is tracked and managed.
Pre formulation
Before the actual trial formulations, pre-formulation is done to gain information about the drug substance.
Their activities include:
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Review of the selected product document Gathering samples of the reference product Evaluating the physical characteristics of the product. Determining reference drug release characteristics Characterization of the drug to determine the form of the drug
Based on these activities, decisions are made according to the formulation type and process of development. The reference product itself determines the dosage form and strength.
Three processes are carried out. They are:
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Direct mixing: The drug substances are directly blended with the excipients. Then the mixture is either compressed into tablets or filled into capsule shells.
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Dry granulation: The drug substances are processed with the excipients using a slugging technique. This is followed by granulation sizing. Finally, the additional excipients are blended with the product. It is then compressed into tablets or filled into capsule shells.
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Wet granulation: In this process, the drug substance is processed with the excipients. Then the binder is mixed with a solvent to form a granulation that is dried and blended with additional excipients. After that, the final mixture is either blended into tablets or filled into capsules.
Whenever possible, direct mixing is initiated because his process is the most straightforward and economical means to produce solid pharmaceutical dosage. The following ingredients are included in a tablet or capsule dosage:
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Chemically active ingredients Binder which helps to hold drug particles to form tablets or capsule slugs Solvent for undergoing wet granulation A disintegrating agent which helps to break apart the granules and tablets for dissolution and absorption
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Anti-adherent which works as a lubricant A lubricant prevents the powders from sticking to the equipment used to compress tablets.
There are some other ingredients as well;
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Dyes which impart a color to the tablet Sweetening agents which add flavors Wetting agents to enhance the solubility of the drug substance Acidifying agents and buffers which provide a more stable environment to the drug product.
After pre-formulation work and development are completed, small scale trials are performed. During the trials, the drug substance is processed with the excipients to produce a dired strength and appearance dosage. The dosage is then physically and chemically evaluated. This determines its acceptability.
Some of the common types of testing performed on the tablets and capsules are:
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Physical testing like appearance, weight variation, time of disintegration, etc.
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Chemical testing like chemical identification, dissolution profiles vs. reference product, etc.
If the product retains good physical and chemical properties, it is sent for the test of “in-vivo bioequivalency” vs. reference product. If it proves to be bioequivalent to the reference product, a package is assembled and submitted to the respective government regulatory agency who reviews the product and approves it eventually. A successfully developed generic product requires bioequivalence study, approval, and product validation study. Spending more time, planning, and effort during generic drug development will generate the type of desired robust products.