Solid Dosage Forms

FAD MPharm2 - Powder Technology to Quality Control

• Course taught by Dr Hao-Ying Li at King's College London
• Focuses on formulation and analysis of drugs (FAD) for MPharm2 students
• Slides adapted from Dr Bahijja Raimi-Abraham

Content Overview - Role of Pharmaceutics from Lab to the Patient

• The content overview covers the role of pharmaceutics from the lab to the patient.
• Key areas include particle size and methods, particle size and state, particle milling, powder granulation, powder mixing and flow, powder technology, quality control of solid dosage forms, solid dosage forms, excipients, traditional tablet manufacturing methods, tablet film coating, and new formulations
• Diagram of the systemic role of pharmaceutics, showing a barrier from the lab to the patient
• Examples of solid dosage forms (capsules) and their roles are examined
• Diagrams depict how materials move through stages from lab or processing to end products

Formulation & Analysis of Drugs (FAD) - Traditional Tableting

• The presentation displays a wide assortment of colorful tablets.
• The material is focused on traditional tableting methods
• It details the advantages and disadvantages of different methods.

Tableting

• This is a heading used in the presentation related to the topic.

Solid Dosage Forms: Traditional Tablet Manufacturing Methods

• Learning outcomes include discussing differences between direct compression and other tabletting methods; describing the process of tablet compaction; discussing how powder properties affect tablet compaction; and discussing common problems during tabletting and their solutions.

What is a Tablet? (Summary: Definition Eur. Ph.)

• Tablets are solid preparations, containing a single or multiple active substances
• Typically obtained by compressing uniform particle volumes.
• May contain excipients.
• May have lines or markings.
• May be coated.

Oral Administration

• Oral administration (p.o.)is where a substance is taken through the mouth.
• Medications taken orally are meant to have a systemic effect by entering the bloodstream
• The process involves various body parts from oral cavity to the intestines and eventually the bloodstream.

Oral Administration (GI)

• Oral administration is a part of enteral administration
• Food and/or drugs are administered to the patient via the gastrointestinal tract.
• It is the most common route of drug delivery due to convenience, cost-effectiveness, and patient acceptability.
• Age or disease related dysphagia and emergency/critical care are potential obstacles to oral administration

Drug delivery to the oral cavity

• Buccal and sublingual drug delivery
• Local and systemic diseases are included
• Advantages are accessibility, removal of the effect, avoiding the first pass effect, fast systemic delivery, and patient acceptability.
• Disadvantages are saliva washing away the drug, small surface area, taste masking requirements, and permeability of the oral mucosa.

Why Tablets for Oral Drug Delivery

• Chemical and physical stability
• Accurate drug dosing
• Convenient handling
• Low cost of manufacturing, packaging, and shipping

How to Make Compressed Tablets

• Compressed tablets are the most widely used solid dosage form
• They must meet physical requirements (hardness, disintegration, friability, and uniformity)
• Granulation (wet/dry) and direct compression (powder mix) are used to achieve tablet characteristics.

How Are Solid Dosage Forms Manufactured

• The steps involve physicochemical characterization, powder processing, and quality control characterization.

Tablet Manufacturing

• Processes for tablet manufacturing (wet granulation, dry granulation, and direct compression). Materials and steps involved for each method are noted.

Wet Granulation

• Benefits include preventing segregation, improving mixing and flow properties, avoiding dustiness, enhancing compressibility, improving appearance, and densifying the material.

Dry Granulation

• Granulation is done without the use of liquids (slugging/roller press methods)
• Used when the ingredients are sensitive to heat or moisture.

Direct Compression

• Excipients, API, blending, and compression are the key processing steps to obtain tablets by this method.

Processing Steps(wet, dry, direct)

• A table compares the processing steps for wet granulation, dry granulation, and direct compression.

Processing of Tablet Manufacturing

• The stages of tablet manufacture, from powder, blending, granulation (Wet/Dry), Sizing, drying, compression, quality control and packaging.

Direct Compression Advantages and Disadvantages

• Advantages include simplified validation, high efficiency, cost effectiveness, reduced strain on API, faster dissolution, and lower microbial contamination.
• Disadvantages include tablet defects (sticking, capping, lamination), restricted excipient choice, lack of appropriate compressibility, and poor flowability or homogeneity.

Types of Tablet Presses

• The distinction between single and multi-station tablet presses, with notes on scale of application(lab-scale or industrial scale).

Modern Tablet Presses

• How modern tablet presses work is being examined in this section of the slides.

Examples of Tablets: Oral Drug Delivery

• Various types of tablets, including conventional (immediate release), conventional (modified release), effervescent, chewable, sublingual/buccal, and lozenges, are highlighted.

Drug-Release Types of Tablets

• Different types of drug release for tablets, including immediate, extended (diffusion, dissolution, erosion, osmotic), and delayed, are detailed.

Type of Tablets: Immediate Release

• Immediate release tablets are designed to deliver the API immediately after administration; no deliberate effort to change release rate.
• Immediate release products result in fast drug absorption and onset.

Type of Tablets: Effervescent Tablets

• Effervescent tablets dissolve in liquid (e.g., water).
• Products of compression of component ingredients into a dense mass.
• The tablets are increasingly popular in various sectors (including supplements and pharmaceuticals) because they are easier to consume.

Type of Tablets: Effervescent Tablets (cont.)

• They are a great alternative for patients with trouble swallowing, especially older adults needing supplements.

Type of Tablets: Immediate Release vs Extended Release

• Focuses on the advantages and disadvantages of immediate vs extended release in terms of patient compliance, side effects, and therapeutic effects (diagram included).

Type of Tablets: Modified Release

• Extended-release (ER) dosage forms allow reductions in drug frequency compared to immediate-release formulations. Other terms such as ER/XR, SR, XL, and CR are also used.

Types of Tablets: Extended Release Tablets

• Different tablet release mechanisms, including diffusion controlled (membrane and matrix), erosion controlled, and osmosis controlled.

Extended Release Tablets: Concerta XL (Methylphenidate)

• Includes a sophisticated 3-phase delivery system providing 12-hour symptom control.

Type of Tablets: Modified Release - Delayed Release

• A dosage form releasing the drug at a time other than immediately after administration. Enteric-coated dosage forms are commonly used for delayed release.

Extended Release Tablets: Paraxyl CR (Paroxetine)

• Details the composition of a controlled-release paroxetine tablet.

Film Coating of Tablets

• Learning outcomes cover taking commercial coated tablets, understanding roles of components, identifying coatings for immediate/modified release, explaining mechanisms of functional coatings, describing coating processes, and discussing common issues encountered.

What Are Coated Tablets

• Coated tablets have layers of substances such as sugars, plasticizers, waxes, and coloring materials.
• Types of coatings include sugar-coated, film-coated, enteric-coated, modified-release coatings.

Why Coat Tablets

• Coating addresses therapeutic (avoiding irritation, bad taste, inactivation) and technological (reducing moisture/dust, improving stability; prolonging shelf life) and marketing considerations (avoiding bad taste, improving appearance, and product identity).

Types of Coating (including Sugar Coating)

• Types of coating include sugar coating, film coating, controlled release coating, compression coating, electrostatic coating, dip coating, vacuum film coating.

Types of Coating: Sugar Coating

• Description of the process and the appearance of tablets with a sugar coating
• The process of multi-stage operations

Types of Coating: Sugar Coating Description

• Steps of multi-stage coating operations: sealing, subcoating, smoothing, colouring, polishing, and printing are explained.

Types of Coating: Sugar Coating Process Explanation

• Details the steps in sealing, subcoating, and other coating processes involving the application of materials, solutions, and drying methods for a consistent coating.

Sugar Coating: Disadvantages

• The process is tedious, requires skilled technicians, and increases tablet size and weight; there's batch-to-batch variability and possible cariogenic potential.

Types of Coating: Film Coating

• Film coating deposition of a thin polymer film, single-stage process, including solvents, polymers, plasticizers, and colourant.

When to Apply Film Coating

• Considerations for masking objectionable taste/odor, controlling drug release, and considering tablet properties during coating design.

Film Coating Process

• Coating liquid containing polymer, plasticizers, and other materials is sprayed onto a rotating tablet bed and dried to create coating film.

Film Coating Process: Drum Coating

• Details drum coating, mentioning that coating liquid is sprayed on a rotating tablet bed.

Film Coating in a Fluidized Bed

• Wurster film coating is mentioned as a method of coating and drying combined in one process in a fluidized bed.

Main Components in a Tablet Film

• Covers film formers, solvents, plasticizers, and colorants/opaquents.

Immediate Release Film Formers

• Immediate release coatings do not alter tablet disintegration, dissolution, or bioavailability.

Functional Coatings: Enteric Film Formers

• An enteric coating prevents dissolution/disintegration in the gastric environment to protect sensitive APIs.

Functional Coatings: Sustained Release Film Formers

• These coatings resist dissolution or disruption at various pH values; drug release is controlled by diffusion.

Ideal Film Former Properties

• Ideal film formers are chemically inert, non-toxic, soluble in solvents, and work well with other excipients.

Film Additives: Plasticizers

• Plasticizers are non-volatile compounds improving film flexibility and handling.

Film Additives: Colourants

• Water-insoluble colorants (pigments) are commonly used; they have advantages over water-soluble ones (better stability, opacity, and impermeability).

Film Additives: Colourants (cont.)

• Colourants are used for identification purposes, patient understanding, and counter-feiting prevention.

Film vs Sugar Coating

• A comparison table of features and characteristics for film and sugar coatings.

Types of Coating

• Lists different coating types (sugar, film, etc.) and the methods to achieve them (compression, electrostatic, vacuum).

Compression Coating

• Compression coating uses compression technique to form a coat of material around a pre-formed core, mostly used to separate chemically incompatible materials, a dry process.

Electrostatic Coating

• A photocopying technology-based electrostatic coating process is used to create distinctive tablet coatings. A charged powder adheres to the tablet.

Vacuum Film Coating

• Vacuum film coating uses a sealed container heated in a water bath under vacuum; solution is sprayed inside and the solvent is evaporated.

Coating Problems and Remedies

• Picking, pitting, chipping, and roughness/orange peel are common coating problems and their solutions (reducing spray, increasing temperature, altering rotation speeds, and adjusting material properties).

Capsules: General and Hard

• Capsules are solid dosage forms composed of a shell and a fill. The advantages are precise dosing, masking taste/odor, customization of formulation, ease of swallowing, requiring fewer excipients. The disadvantages are limited capacity for high-dose drugs, moisture sensitivity and need for specialized manufacturing.

Hard Capsules

• What hard capsules are, what they contain, how they are made, and their advantages/limitations.

Solid Dosage Forms: Hard Capsules

• Learning outcomes detail taking commercial hard capsule products, analyzing inactive ingredients, explaining roles of components, comparing tablets and capsules, describing hard capsule manufacture, and analyzing fill properties.

Capsules (general)

• Describes the concept of capsules: solid dosage forms enclosing medications; advantages (precise dosing, masking, customization, ease of swallowing, fewer excipients); disadvantages (limited capacity, moisture-sensitivity, equipment requirement).

Hard Gelatin Capsules: Sizes

• Data related to capsule sizes (diagram with sizes) and volumes. Includes real-world application in pre-clinical animal studies.

Hard Gelatin Capsules: Sizes (cont.)

• Diagrams showing variations in sizes of hard capsules.

Composition (Gelatin, Polymers)

• Gelatin (bovine, porcine, fish), and alternative polymers (HPMC, pullulan).

Capsule Polymers for Coni-Snap®: Gelatin

• Discusses gelatin as a frequently used capsule material derived from collagen, a connective tissue protein in mammals.

Diagram of Gelatin Structure

• Gelatin is a self-gelling agent and a good film-forming polymer; cooling above a minimum critical concentration results in a three-dimensional gel network.

Capsule Polymers

• Hypromellose (also called hydroxypropyl methylcellulose, or HPMC) and pullulan are categorized as capsule polymers.

Coni-Snap Gelatin Capsules

• Describes features of coni-snap gelatin capsules including the tapered rim for effortless opening, snap lock system for leak-proofness. Air vents that ensure efficient filling, and rounded ends for durability.

How Are Hard Capsule Shells Made?

• Discusses the stages involved in hard capsule shell production: gel solution preparation, capsule dipping, and capsule drying.

General Overview of Filling Process

• Details the procedure/machine used for filling capsules.

Advantages of Hard Capsules (Combinations)

• Hard capsule advantages are highlighted, particularly when combining single and multiple active compounds with diverse coatings, such as extended-release, and combinations of drugs.

Advantages of Hard Capsules (Dry Powder Inhalers)

• Dry powder inhalers use capsules for ease of handling, improving pulmonary availability, allowing for patient-controlled dose administration, and suitability for various active compounds (e.g., peptides like insulin).

Capsules Preferred by Patients

• Patient preferences favoring capsules (over tablets or uncoated tablets) are described via survey data. The primary reason relates to the masking of taste/odor, and a smooth, rounded shape for easy swallowing.

Capsules Help Improve Patient Compliance

• Patient compliance is enhanced by capsules due to the convenient form (masking taste/odor, easy to swallow), aiding in proper dosing (identification characteristics such as colour).

Soft Capsules or Softgels

• Information on what soft capsules are, what they contain, how they are made, and their advantages/limitations

What Are Soft Capsules (cont.)

• Describes the one-step formation, filling, and sealing process of soft capsules, resulting in a complete hermetically sealed capsule. Softgels (soft capsules) are regarded as a superior oral drug delivery format compared to other solid dosage forms.

Benefits of Soft Capsules

• Excellent dosage precision, enhanced stability/long shelf life (minimal degradation, light/oxygen influence), organic certification for various ingredients, wide range of ingredients, shapes/sizes, ease of swallowing, and neutral flavour/taste.

Rotary Die Method of Manufacturing Soft Capsules

• Describes the rotary die method that's part of soft capsule manufacturing; involves intricate processes of mixing and spreading components. Shows schematic diagrams from various stages.

Rotary Die Method of Manufacturing Soft Capsules (cont.)

• Shows different stages of the process, including components like feeder rolls, ribbon guides, and filling processes. The diagram for soft gel or soft capsule production via rotary die process is shown.

Globex Seamless Method of Manufacturing Soft Capsules

• The globex process, a seamless method for soft capsule manufacturing; this process involves heating gelatin with plasticizers and dyes, then incorporating the drug in gelatin droplets and cooling the oil for gelatin solidification.

Content Overview - Schedule of Topics

• Lists the days and dates associated with topics being covered in the course. Multiple topics are listed for each day and are related to the categories of powder technology and solid dosage forms.

General

• This is a general heading that doesn't indicate a specific subtopic in the provided material.