Solid Oral Dosage Form I PDF

PR5217 Formulation Science L07. Solid Oral Dosage Form I DUN JIANGNAN, Ph.D. AY24/25.S1 10-OCT-2024  Dr. Dun Jiangnan [email protected] Office: S9 15-01F Office hour: By appointment only...

PR5217 Formulation Science L07. Solid Oral Dosage Form I DUN JIANGNAN, Ph.D. AY24/25.S1 10-OCT-2024  Dr. Dun Jiangnan [email protected] Office: S9 15-01F Office hour: By appointment only Response is usually expected in 1-2 days, if not, please remind me!!!! No more than 3 questions per email. If you have more questions, feel free to schedule a meeting with me to clarify. Learning Outcomes Familiarize with the advantages in tablets. Familiarize with the commonly used tablet excipients, and their important properties in solid formulation. Important concept Pharmaceutics Pharmaceutics converts a drug into a medicine. Understanding of the basic physical chemistry necessary for the e ective design of dosage forms (physical pharmaceutics); Design and formulation of medicines (dosage form design); Manufacture of medicines on a small (compounding), intermediate (pilot-scale) and large (manufacturing) scales; Product performance testing (physical, dissolution, stability). ff Design of Solid Dosage Forms Preformulation The consideration of steps that need to be performed before formulation development can begin. Studies A full understanding of the physicochemical properties of drugs and other ingredients in a dosage form and how they may interact. Data gathered will in uence the design of the future dosage form. PR 5225 next semester fl Design of Solid Dosage Forms Formulation Small and large scale manufacture, and the advantages, disadvantages and characterization of the wide range of available dosage forms. The properties of these dosage forms can be modi ed dependent on the properties of the materials included, the route of drug administration and speci c patient needs. fi fi Drugs in Solid State Drugs in the solid state can be administered simply as powders. Metered Dose Inhalers (MDIs) Drugs in Solid State They are more usually formulated as the following solid oral dosage forms： Tablets Capsules Learning Plan Week 8 Introduction, Tablets I Week 9 Tablets II, Capsules I Quiz 1 (CANVAS) Week 12 Capsules II, Mini-Review Quiz 2 (CANVAS)  Tablets The oral route is a convenient and safe way of drug administration. Compared with liquid dosage forms, tablets have better chemical, 70% physical and microbiological stability of the dosage form. The preparation procedure enables accurate dosing of the drug. Tablets are convenient to handle and can be prepared in a versatile way with respect to their use and the delivery of the drug. Tablets can be mass-produced relatively cheaply, with robust and quality-controlled production procedures giving an elegant preparation of consistent quality. medicines are administrated as tablets Types and Uses of Tablets Regular IR tablets Orally Disintegrating Tablet Chewable tablets Modi ed Release tablets Sublingual tablets and buccal tablets fi  Quality Attributes Like all dosage forms, tablets should ful ll a number of product quality attributes regarding chemical, physical and biological characteristics. Critical Quality Attributes (CQAs) are those that have great impact on the safety and ef cacy of drug product. Content Uniformity Disintegration time Tensile strength Dissolution How about the taste? Friability … fi fi Tableting R&D: Lab-scale instrument Zwick Presster Styl’One Manufacturing of Tablets: The Rotary Press Fully programmable and extremely high e cient -> High Speed Tableting ffi Toolings Tablets are formed in a variety of shapes. The most common tablet shapes are circular, oval and oblong, but tablets may also have other shapes, such as triangular or quadratic. From a side view, tablets may be at or convex and with or without bevelled edges. Tablets may also bear break marks or symbols and other markings. fl Tablets Formulation Development (3W) Drugs + Excipients What kind of drugs? What kind of excipients? Pre-formulation considerations Chemical nature, Functionality, (PR 5225) Quantity, etc. What kind of manufacturing technologies? Example: A Standard IR Tablet Formulation Quantity Materials Category Functionality (mg) Celecoxib 49.3 API API Identifying the main functionality of Avicel PH 102 79.2 Excipient Filler/Diluent important materials is required. SuperTab 11SD 32.5 Excipient Filler/Diluent Knowing the commercial name of MgSt 2.1 Excipient Lubricant commonly used excipients is required. Aerosil 200 4.2 Excipient Glidant Ac-Di-Sol 802 10.7 Excipient Superdisintegrant What is a more ef cient way to visualize the Total tablet weight: 178 mg formulation components? fi Example: A Standard IR Tablet Formulation Materials Amount (%) Category Functionality Celecoxib 27.7 API API Avicel PH 102 44.4 Excipient Filler/Diluent SuperTab 11SD 18.3 Excipient Filler/Diluent MgSt 1.2 Excipient Lubricant Aerosil 200 2.4 Excipient Glidant Ac-Di-Sol 802 6.0 Excipient Superdisintegrant Total: 100% Percentage is more commonly used in tablets formula  Filler/Diluent A must-have component in typical Pharmaceutical Tablets Increase tablet volume or weight Significant % of the dosage form Overcome the poor properties of API Successful/robust manufacturing and dosage form performance may heavily depend upon llers’ properties. Critical properties: Powder flow, Tablet strength Desired performance: Content uniformity, disintegration time, dissolution, friability, and physical/chemical stability fi Example 1: Microcrystalline Cellulose (MCC) MCC is widely used as a ller in oral tablet formulations MCC can also be used as a dry binder in granulation processes Other functionality: MCC is considered self-lubricated Exhibits low ejection force, eases the tablet ejection MCC is a wood ber, which will be swelling upon contact with water Can facilitate tablet disintegration fi fi Crystalline and Amorphous Structure of Cellulose MCC exhibits birefringence when observed under polarized light microscopy but is PXRD partially amorphous due to the small size (nanometers) of crystalline domains. MCC is NOT pure crystalline, and has amorphous regions Multiple Grades of MCC Avicel PH101 Avicel PH105 The main di erence between di erent grades of MCC is their particle size distribution. Ranking of the primary particle size: Avicel PH105 < Avicel PH101 < Avicel Avicel PH102 Avicel PH200 PH102 < Avicel PH200 Avicel PH105 has the lowest primary particle size and it is the most cohesive one among the above 4 grades. FMC Biopolymer ff ff Mechanical Properties of MCC Plastic MCC is a very plastic material, which easily undergoes plastic deformation even at very low compaction pressures. Any disadvantages? MCC has excellent mechanical properties, and it’s commonly used to overcome the poor mechanical properties of drugs. The mechanical properties of MCC is very sensitive to the RHs. Selection of Excipient: MCC Drug Example 2: Lactose Monohydrate (LM) Lactose monohydrate is primarily used as a ller/diluent in tablet formulations. Pharmatose 125M SuperTab 30GR Due to the rough surface, LM generally exhibits a much higher ejection force than MCC fi Mechanical Properties of LM Brittle LM has been manufactured in many grades, with di erent particle sizes, shapes, and surface properties. Unlike MCC, LM undergoes extensive fragmentation during the powder copmpaction. Fragmentation continues creating new fresh surfaces ff  Lubricant: Magnesium Stearate (MgSt) MgSt is a very commonly used tablet lubricant. High lubrication efficiency Economy Lapham et al. Powder technol. 2019 (342), 676-689 11 Disadvantages of MgSt Diverse origins Hydrophobic Deterioration of Chemical impurities tablet qualities Poor flowability Phase impurities (Cohesive) 12 MgSt may negatively impacts the MP 18 Lubrication with MgSt Delays Tablet Dissolution …… 13  Disintegrant/Superdisintegrant A disintegrant is included in the formulation to ensure that the tablet, when in contact with a liquid, breaks up into small fragments, which promotes rapid drug dissolution. Glidant The role of the glidant is to improve the owability of the powder. Glidants are used in formulations for direct compaction but are often also added to granules before tableting to ensure that su cient owability of the tablet mass is achieved for high production speeds. For modern glidant such as Aerosil 200, a fumed silica (silicon dioxide),