New Rule on Bulk Substances for Compounding Drugs Proposed by FDA?

New Rule on Bulk Substances for Compounding Drugs Proposed by FDA?

🏓The FDA issued a proposed rule adding six bulk drug substances to the list of materials that can be used in compounding, while removing four substances.

🏓In addition, the agency is proposing to use a new set of four criteria when evaluating substances for inclusion🏓 The FDA will consider each criterion on a substance-by-substance basis, including:

🔑The physical and chemical characterizations of the substance🔑Any safety issues raised in using the substance in compounded drug products🔑The available evidence of effectiveness or lack of effectiveness of a drug product compounded with the substance🔑if any such evidence exists, and historical use of the substance in compounded drug products🔑 including information about the medical conditions the substance has been used to treat🔑 and any references in peer-reviewed medical literature

Preparation of MFR for Pharmaceuticals

Preparation of MFR for Pharmaceuticals:

Step by step procedure to write a master formula record (MFR) for pharmaceutical products.

Master formula record (MFR) is a master document for any pharmaceutical product. It contains all information about the manufacturing process for the product.

MFR is prepared by the research and development team of the company and all other documents like BMR and BPR are prepared using MFR by the manufacturing units.
MFR should have following parts:
1. Product Details: First of all on the first page following details about the product are added.
Name, logo and address of the manufacturing company
Dosage form name
Brand name
Generic name
Product code
Label claim of all ingredients
Product description
Batch size
Pack size and packing style
Shelf life
Storage conditions
MFR number and date
Supersede MFR number and date
Effective batch number
Authorization by the production and quality assurance head
2. Flow Chart: Steps of the manufacturing process to be monitored. Flow chart of the material movement from dispensing to the final product to stores.
3. Equipments: Create a list of all required equipments and machines required in the manufacturing process with their capacity.
4. Special instructions: Write down the precautions special instructions to follow during the product manufacturing and packing and these should also be added in the batch manufacturing formula. Batch manufacturing formula should include the following.
Name of ingredients with test reference (As IP, BP, USP etc.)
Quantity to be added
Overages to be added (%)
5. Calculations: Include the calculation steps of all active materials to get the 100% of the active material. Calculation shall be done using water content or LOD to get 100% potency.
6. Manufacturing Process: Write all steps in all stages of the manufacturing process. All process steps like shifting, milling, mixing, lubricating, granulation, compression and coating should be written in detail including the process time and yield. Include atmospheric conditions as temperature, humidity and storage conditions for every step.
7. Packing Process: List of all packing materials with their quantity is written. Line clearance, reconciliation of printed and unprinted packing materials should be included in details.
8. Yield: Include the theoretical, actual yield and acceptance limit of the batch.

Detail given above should be included in a general master formula record. Other details should be added as per company requirements in the master formula record.

Tablet properties

Tablet properties

👉Tablets can be made in virtually any shape, although requirements of patients and tableting machines mean that most are round, oval or capsule shaped👉 More unusual shapes have been manufactured but patients find these harder to swallow, and they are more vulnerable to chipping or manufacturing problems.

👉Tablet diameter and shape are determined by the machine tooling used to produce them – a die plus an upper and a lower punch are required👉 This is called a station of tooling👉The thickness is determined by the amount of tablet material and the position of the punches in relation to each other during compression👉Once this is done, we can measure the corresponding pressure applied during compression👉The shorter the distance between the punches, thickness, the greater the pressure applied during compression, and sometimes the harder the tablet👉Tablets need to be hard enough that they don’t break up in the bottle, yet friable enough that they disintegrate in the gastric tract.

👉Tablets need to be strong enough to resist the stresses of packaging, shipping and handling by the pharmacist and patient👉The mechanical strength of tablets is assessed using a combination of (i) simple failure and erosion tests, and (ii) more sophisticated engineering tests👉The simpler tests are often used for quality control purposes, whereas the more complex tests are used during the design of the formulation and manufacturing process in the research and development phase. 👉Standards for tablet properties are published in the various international pharmacopeias (USP/NF, EP, JP, etc.). The hardness of tablets is the principle measure of mechanical strength👉 Hardness is tested using a tablet hardness tester. The units for hardness have evolved since the 1930s, but are commonly measured in kilograms per square centimeter. Models of tester include the Monsanto (or Stokes) Hardness Tester from 1930, the Pfizer Hardness Tester from 1950, the Strong Cob Hardness Tester and the Heberlain (or Schleeniger) Hardness Tester.

👉Lubricants prevent ingredients from clumping together and from sticking to the tablet punches or capsule filling machine👉 Lubricants also ensure that tablet formation and ejection can occur with low friction between the solid and die wall, as well as between granules, which helps in uniform filling of the die.

👉Common minerals like talc or silica, and fats, e.g. vegetable stearin, magnesium stearate or stearic acid are the most frequently used lubricants in tablets or hard gelatin capsules

Manufacture of the tableting blend

Manufacture of the tableting blend.

👉In the tablet pressing process, the main guideline is to ensure that the appropriate amount of active ingredient is in each tablet👉Hence, all the ingredients should be well-mixed👉If a sufficiently homogenous mix of the components cannot be obtained with simple blending processes, the ingredients must be granulated prior to compression to assure an even distribution of the active compound in the final tablet👉Two basic techniques are used to granulate powders for compression into a tablet: wet granulation and dry granulation.
👉Powders that can be mixed well do not require granulation and can be compressed into tablets through direct compression.

Tablet manufacturing in what is Dry granulation?

✍Tablet manufacturing in what is Dry granulation?

👉Dry granulation processes create granules by light compaction of the powder blend under low pressures👉The compacts so-formed are broken up gently to produce granules (agglomerates). 👉This process is often used when the product to be granulated is sensitive to moisture and heat👉Dry granulation can be conducted on a tablet press using slugging tooling or on a roll press called a roller compactor. 👉Dry granulation equipment offers a wide range of pressures to attain proper densification and granule formation👉 Dry granulation is simpler than wet granulation, therefore the cost is reduced👉 However, dry granulation often produces a higher percentage of fine granules, which can compromise the quality or create yield problems for the tablet👉 Dry granulation requires drugs or excipients with cohesive properties, and a ‘dry binder’ may need to be added to the formulation to facilitate the formation of granules.
✍Tablet manufacturing in what is Granule lubrication?

👉After granulation, a final lubrication step is used to ensure that the tableting blend does not stick to the equipment during the tableting process. This usually involves low shear blending of the granules with a powdered lubricant, such as magnesium stearate orstearic acid.