Tablets PDF

Tablets Source Ansel HC, Popovich NG. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems. 12th ed. Jr. LVA, Popovich NG, Ansel HC, editors. Lippincott Williams & Wilkins; 2023. Chapter: Tablets Learning objectives Differentiate between the various types of tablet dosage for...

Tablets Source Ansel HC, Popovich NG. Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems. 12th ed. Jr. LVA, Popovich NG, Ansel HC, editors. Lippincott Williams & Wilkins; 2023. Chapter: Tablets Learning objectives Differentiate between the various types of tablet dosage forms – unique properties, applications, and methods of preparation. Describe the typical manufacturing processes and equipment for compressed tablets; discuss the challenges, common problems, and material requirements. Explain the purposes of granulation; compare and contrast wet vs. dry granulation. Explain the purpose of tablet coating; compare and contrast sugar, film, and gelatin coating. Learning objectives List the commonly used excipient categories in tablet formulations; explain their functions and provide examples. Recommend a suitable tablet dosage form for a given drug and/or patient. Compare and contrast capsule vs. tablet dosage forms. Recognize other oral solid dosage forms and their applications. Definition How many pills are in the jar? Pills vs. Tablets Pills are shaped like a small round ball It's the earliest form after powders were made into solid dosage forms to dispense to patients Easier to take, at present obsolete, no longer in use in modern western medicine But the term stuck so it is used in general for most non-powder oral solid dosage forms e.g. tablets, capsules etc. Pills vs. Tablets Tablets are often flat and circular, but may have a variety of shapes and sizes Tablets Definition Tablets may be defined as the solid unit dosage form of medicament or medicaments with or without suitable excipients and prepared either by molding or by compression. Applications Usually taken orally But can be designed for sublingual, buccal, rectal or intravaginal administration Reading Assignment Ansel, Chapter 8: Tablets, Section: “Types of Tablets” Compressed tablets Orally disintegrating tablets Multiple compressed Coated Chewable tablets Molded tablets Effervescent tablets Immediate-release tablets Vaginal tablets Modified-release tablets Hypodermic tablets Sublingual/buccal tablets Dispensing tablets Compressed Tablets Prepared by tablet presses with special tooling Die Upper punch Lower punch Various shapes and sizes Die cavity design Punch tip design Typical wt range: 50 – 1000 mg Common Designs Imprinting Required by FDA, effective 1995 For all solid dosage forms for human use Product specific ID codes Can be embossed, debossed (engraved), or printed Tablet Compression – Key Steps 1. Fill powder in die cavity 2. Remove excess powder 3. Compress tablet Upper 4. Eject tablet Punch Die Lower Punch Step 1 Step 2 Step 3 Step 4 Powder to Tablet – How? Tableting is a COMPACTION process and involves two steps… 1. Compression Reduction in bulk volume by eliminating voids and bringing particles into closer contact. 2. Consolidation Increased mechanical strength due to inter-particulate interactions (bond formation) Compaction = Compression + Consolidation Good compressibility Adequate bonding Minimal elastic recovery Bonding Mechanisms Five types (Rumpf classification) 1. Solid bridges - due to melting, crystallization, etc. 2. Binder bridges – due to dry binders 3. Mechanical interlocking – due to particle shape 4. Intermolecular forces – van der Waals, electrostatic, hydrogen bonds, etc. 5. Immobile liquid bridges – due to binders used during granulation, e.g. PVP Tablet Compression – Equipment Single-station tablet press Manual Automatic Multi-station rotary tablet press Rotary Tablet Press Tablet Formulation – Design Goals Accurate dosage Good bioavailability Ease of production Extremely fast Stability No capsule shell to protect the formulation Elegance No capsule shell to hide non-elegant formulation Compare to capsule formulation? Tablet Formulation – Challenges Material requirements for high speed compression Good to excellent flowability Consistent density Uniform mixture Adequate compactibility No adhesion to metal tooling Compare to capsule formulation? Common Tableting Problems Capping Complete or partial separation of the upper or lower surface of the tablet horizontally, when the tablet comes out of the die Air entrapment? Insufficient binding? Sticking? Common Tableting Problems Lamination Similar to capping but here the tablet gets separated into layers Air entrapment? Tableting speed? Common Tableting Problems Chipping Chipping usually happens around the tablet surface, small pieces are broken out or chipped out of the tablet Improper machine setting? worn out tooling? Common Tableting Problems Picking and Sticking Picking Picking occurs when a part of the tablet sticks to the punch surface and gets eroded from the tablet surface Mostly happens with the upper punch. May lead to weight variation too Sticking Sticking of the tablet material with the die walls or with each other Increased ejection forces May cause production of tablets with rough edges Common Tableting Problems Mottling Uneven distribution of the color on the surface of the tablet, with dark and light patches on it It is mainly due to different coloration of the excipient or the degradation product of a formulation component is colored Common Tableting Problems Bridging and double-impression Common Tableting Problems Coating related problems Orange-peel, blooming, blistering, cracking Manufacturing – Capsule Filling Methods Other problems Weight variation Content uniformity Tablet strength Reading Assignment Ansel’s, Chapter 8: Tablets Compressed Tablet Manufacture, pp 276 – 282 Focus on these questions: 1. What are the three basic methods for tablet preparations? What are the pros/cons for each method? 2. What are the purposes for granulation? 3. What are the commonly used excipient categories for tablet products? Explain their functions and provide examples. Build on the previous excipient list for capsules. Tablets - Methods of Manufacture Direct Compression (DC) Tablets - Methods of Manufacture Most powder mixtures are not suitable for direct compression May require wet-granulation (WG) or dry-granulation (DG) prior to tableting Blending API + Excipients WG DG DC Lubrication Tableting or Encapsulation Granulation A particle size enlargement process after which the initial primary particles can still be identified Agglomerates, NOT Aggregates Purpose? ↑ Flowability ↑ Density ↓ Segregation Wet Granulation 1. Mix ingredients API, filler, binder, and disintegrant 2. Prepare a damp mass Add water or binder solution In an agitated mixer or fluid-bed system 3. Dry the granulation 4. Screen the granulation 5. Blend-in lubricant 6. Ready for tableting Wet Granulation Dry Granulation 1. Mix ingredients API, filler, binder, and disintegrant 2. Compact into large pieces Slugging Roller compaction 3. Screen the granulation 4. Blend in lubricant 5. Ready for tableting Dry vs. Wet Granulation Which process yields better materials for tableting? WG Which process gives higher throughput? DG Which process is suitable for drugs which are sensitive to heat or moisture? DG Ideal Tablet Properties What is an ideal tablet size range? 10 – 1000 mg What is an ideal drug loading range? 10 – 50 % What is an ideal range for tablet dose strengths? 10 – 500 mg Challenging Examples High tablet strength Nootropil® Tablet 1200 mg actives in each tablet Main challenges? API properties dominate Poor flowability Poor compactibility Low tablet strength Synthroid® Tablets 25 – 300 mcg strength Main challenges? Uniformity issues Excipients Definition ‘Any component other than the active principle added intentionally to the medicinal formulation’ or ‘Everything in the formulation except the active drug’. Why add excipients? 1. Improve processing (processing aids) Flow, compressibility, prevent processing issues 2. Enhance aesthetics Color, branding 3. Optimize product performance Modify drug release 4. Facilitate patient compliance Taste masking, odor masking Excipients for Tablets Classification by function (some may have more than one) Processing agents Performance modifiers Fillers (diluents) Drug-release modifying agents Binders Functional coatings, matrix agents Lubricants Glidants Modifying dosage form behavior in vivo Aesthetic enhancers Disintegrants Colors Effervescent / floating systems Flavors / taste masking agents Bioadhesives Coating agents Excipients for Tablets Fillers Imparts bulk or volume to tablet formulations Commonly used for highly potent / low-dose drugs E.g. Lactose, celluloses, dibasic calcium phosphate Binders Provide binding or cohesiveness to formulation blends Powders → binder → granules → binder → compact E.g. Polyvinyl pyrrolidone (PVP), Hydroxypropyl cellulose (HPC) Excipients for Tablets Lubricants Reduce the friction between the tablet components and the tooling (dies and punches) Form an intermediate layer between the tablet constituents and the die-wall Facilitate the ejection of tablet from die cavity and reduce the ejection force May help reduce incidences of sticking and picking of tablets E.g. Magnesium stearate (gold standard) Excipients for Tablets Glidants Improve the flow of the formulation Lower the inter-particulate friction by interposing their particles between formulation granules E.g. Colloidal silicon dioxide (fumed silica) Excipients for Tablets Colorants (pharmaceutical colors) Facilitate identification Enhance the aesthetic appearance of the product Colorants are available in two forms: Soluble (dyes) E.g. FD&C Yellow 5 and 6 Insoluble (pigments/lakes) Dyes dispersed/adsorbed on an inert substrate e.g. Aluminum hydroxide. E.g. FD&C Blue 1 and 2 Certified by the FDA Natural colors? Better? Sterile drug products are NOT colored Excipients for Tablets Flavoring agents Improve the palatability of the tablets. Typically used in chewable, oral disintegrating, buccal tablets Most commonly used flavoring excipients Sweetening agents Others Excipients for Tablets Drug-release modifying agents Modify the release of API from the tablets Two types: Enteric coating agents Release the drug in small intestine, avoid drug release in stomach. Controlled-release excipients Added as coatings and/or within the tablet matrix E.g. Celluloses, Acrylic acid polymers, Polyethylene oxide (PEO) Excipients for Tablets Disintegrants Disintegration is pre-requisite for rapid dissolution and release of drug. Compact → disintegrant → granules → disintegrant → powder E.g. Starch, Sodium starch glycolate, cross-linked PVP Excipients for Tablets Effervescent / floating agents Based on acid-base reaction and in situ formation of gas e.g. CO2 Citric acid, ascorbic acid, tartaric acid Carbonates, bicarbonates of calcium, sodium, potassium etc. Dissolve in water before administration Keep in original packets Do not swallow or chew directly Excipients for Tablets Bioadhesive/mucoadhesive agents Mainly polymeric in nature Chitosan, carbomers, polycarbophil, polyethylene oxide Tablet Coating Why coat a tablet? Protection From environment e.g. moisture From mechanical damage e.g. handling, packaging From ingredient interaction Aesthetic Taste and odor masking Improving product identification and appearance Functional (modifying drug-release characteristics) Extended-release e.g. controlled-release Site-specific delivery e.g. enteric coating Tablet Coating Techniques Film coating For tablets, multi-particulates, capsules Gelatin coating Sugar coating Sugar syrup Compression coating Dry coating, tablet press Tablet Coating Techniques Film coating Thin, polymer coating Durable Colored or clear Coating reveals embossment/debossment In a coating pan or fluid bed Tablet Coating Techniques Gelatin coating Also called GELTABS or GELCAPS Coated with two sheets of gelatin or gelatin shells by a cold-shrink process Made to look like a capsule (denser → smaller) Easier to swallow Tamper-resistant Multiple Compressed Tablets Multi-layer tablets Compression coated tablets (a tablet within a tablet) Purpose: aesthetics, compatibility, staged drug release E.g. Allegra D (bi-layered tablet) 60 mg fexofenadine HCl for immediate release and 120 mg pseudoephedrine HCl for extended release Molded Tablets Prepared in a mold Traditional process – wet massing, extrusion, and air drying New process – heating only Also called tablet triturates Dissolve rapidly in saliva w/o chewing or liquid Easy to swallow Can be used for intra-oral delivery Sublingual/buccal Tablets Fast onset & no first-pass metabolism Orally Disintegrating Tablets (ODTs) Prepared by Molding Soft compression 3-D printing? Disintegrate or dissolve rapidly ≤ 30 sec in saliva w/o chewing or liquid Easy to swallow Can be used for intra-oral delivery Sublingual/buccal Tablets Fast onset & no first-pass metabolism Chewable Tablets Usually compressed tablets Disintegrate in the mouth with or without chewing No water needed, easy to swallow Typically intended for drug absorption in GI Other Oral Solid Dosage Forms Slow drug release for extended local or systemic effect Troches Lozenges Lollipops Films Gummies Other Oral Solid Dosage Forms Limitations Low drug loading Taste Special excipients Unique processes Drug compatibility/stability Can you formulate Acetaminophen into a thin film?