Solid Oral Dosage Forms III

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Questions and Answers

What is the primary reason for using formaldehyde in capsule formulation?

To increase the moisture content of the capsule

To cause a cross-linking reaction that makes the capsule insoluble (correct)

To enhance the gelatin's flexibility

To ensure the capsule dissolves quickly

Which factor is most important for achieving uniform filling in capsules?

Moisture absorption

Particle size distribution

Good powder flow (correct)

Chemical reaction time

In the context of filling capsules, which of the following properties of a powder is least relevant?

Flowability

Color intensity (correct)

Bulk density

Hygroscopicity

How does hypromellose affect capsule formulation?

It softens and distorts the capsule upon moisture absorption Signup and view all the answers

What does the Carr Index primarily reflect regarding powders?

The flowability and compressibility of the powder Signup and view all the answers

Which type of liquid is commonly used in softgel formulations for its limited solubility?

Triglyceride oils Signup and view all the answers

Which component is most frequently used as a hydrophilic liquid in softgel formulations?

Polyethylene glycol Signup and view all the answers

What characteristic do SEDDS improve in drug formulations?

Pharmacokinetic characteristics Signup and view all the answers

Which of the following describes the size range of droplets that form a nanoemulsion?

Less than 200 nanometers Signup and view all the answers

What is necessary for a microemulsion to form in the gastrointestinal tract?

A combination of lipid components and surfactants Signup and view all the answers

What role does hygroscopicity play in capsule formulation?

Hygroscopicity can lead to moisture absorption, affecting the integrity and dissolution of the capsule contents. Signup and view all the answers

Describe how powder flow behavior impacts capsule filling.

Powder flow behavior affects uniformity in filling and can determine the reliability of machines measuring powder volumes. Signup and view all the answers

How do interparticulate interactions influence the compressibility of powders in capsule formulation?

Interparticulate interactions determine how well powders compact under pressure, impacting density and flow characteristics. Signup and view all the answers

What considerations are critical for excipient selection in powder formulations for capsules?

Excipient selection must consider the properties of the active pharmaceutical ingredient (API) and the desired capsule size. Signup and view all the answers

Explain the significance of the arch and rathole phenomena in powder flow.

The arch and rathole phenomena can lead to erratic flow and hinder proper filling, affecting uniformity and stability. Signup and view all the answers

Study Notes

PR5217 Formulation Science - L09. Solid Oral Dosage Form III

Course title: PR5217 Formulation Science
Module: L09. Solid Oral Dosage Form III
Instructor: Dun Jiangnan, Ph.D.
Academic year/Semester: AY24/25.S1
Date: 7-NOV-2024

Learning Outcomes

Capsules (hard and soft) are important solid oral dosage forms.
Understanding typical components and properties of hard and soft capsules.
Understanding formulation considerations for hard and soft capsules.

Pharmaceutical Capsules

"Capsule" is derived from Latin capsula (small box).
Used for many objects, from flowers to spacecraft.
Solid dosage forms with medicinal agents or inactive substances enclosed in a shell (usually gelatin).

Hard Capsules

Popular solid oral dosage form.
Two-piece design: cap and body.
Body fits inside the cap.
Design features: body, shoulder, locking rings, tapered rings, dimples, hemispherical ends, mouth diameter, air vents, and chamfering ring.
Good patient adherence aided by color, easy-to-swallow shape, and a shell masking the taste.

Raw Materials (Shells)

Gelatin is the main component for hard capsule shells.
Hypromellose is used in some new products (e.g., dry powder inhalers).
All polymer systems need non-toxic materials readily soluble in biological fluids and good film-forming properties.
Gelatin is a substance of natural origin (hydrolysis of collagen).
Hypromellose is made from cotton linters or wood; treated with sodium hydroxide and chemicals to produce different viscosity grades.

Capsule Sizes

Hard capsules come in standard sizes 0 to 4.
"Elongated sizes" are 10% larger.
Body volumes vary with size.
Fill weight for powders calculated by multiplying body volume by tapped bulk density.
Fill weight for liquids is calculated by multiplying specific gravity of liquid by capsule body volume by 0.9 (to avoid overflow).

Bulk Density and Tapped Density

Bulk density = weight / original volume (V₀)
Tapped density = weight / final tapped volume (V_f)
Change in packing volume due to void space diminishing and consolidation.

Capsule Shell Filling

Hard capsules can hold various materials with different properties.
Materials must not react with gelatin/alternative shells.
High level of free moisture is not allowed.
Fill volume must not exceed capsule size.
Gelatin and hypromellose are relatively inert materials.
Avoid substances that react with gelatin (e.g., formaldehyde), interfere with shell integrity (e.g., high free water content).

Formulation Considerations in Hard Capsules

Capsules must be filled uniformly for stable products.
Should release active contents for absorption.
Should comply with pharmacopoeial and regulatory authorities (e.g., dissolution tests).
Most products are formulated as powders mixed with excipients (e.g., diluents, lubricants, glidants, wetting agents, disintegrants, stabilizers).
Excipient selection depends on API property and capsule size.

Formulation for Filling Powders

Factors affecting uniform filling: hygroscopicity, flowability, particle size distribution, bulk/tapped density, adhesion/cohesion.
Good powder flow crucial for machines utilizing volume measurement.

Flow Behaviors

Erratic flow (e.g., rathole, arch) vs. funnel/mass flow.
Mass flow—first-in, first-out, reduced segregation

Carr Index and Hausner Ratio

Based on bulk and tapped density of powders.
Predict compressibility propensity.
Free-flowing powders have small differences between bulk and tapped densities.

Formulation for Release of API

First stage: capsule shell disintegration in suitable liquid (e.g., body temperature).
Gelatin capsules dissolve within a minute, and contents release before full dissolution.
Hypromellose capsules tend to take longer to break initially, but then disperse faster afterwards.

Effects of d50 (fills) on the Rate of Absorption

Smaller particles lead to higher peak blood levels due to higher dissolution rate (greater surface area).

Effects of Diluents on the Rate of Absorption

Diluents are generally inactive materials.
Change in diluent (e.g., from calcium sulfate to lactose) can significantly affect API bioavailability.
Lactose provides higher blood drug levels because it is readily soluble.

Effects of Lubricants on the Rate of Dissolution

Some lubricants (e.g., magnesium stearate) may reduce dissolution rate due to poor wetting of the powder mass.
Alternative hydrophilic lubricants can improve dissolution rate.

Formulation for Position of Release

Capsule formulation can be modified for release at specific parts of the GI tract (lower GI tract, small intestine, etc.).
Selecting appropriate locations to maximize API absorption is crucial.
Techniques can be used to alter release profiles (e.g., enteric coating).

Softgels

Softgels contain liquid/semisolid preparations in a single-step encapsulation process.
Convert liquid/semisolid drugs to solid dosage form.
Used for 40% of approved drugs (and 90% of drugs currently under development pipelines).
Often used for poorly water-soluble drugs

Different Softgels Formulations

Components of gelatin shell (gelatin, plasticizer, water)
Various components inside the shell: solution, suspension of drugs, lipophilic/hydrophilic fill matrixes, film coating, etc.
Recent developments include self-emulsifying/nanoemulsions.

Softgels Drug Delivery Systems

Categories of softgels: orally-administered, chewable, twist-off, and suckable.

Key Features and Advantages of Softgels

Improved drug absorption compared to tablets.
Easy-to-swallow.
Avoids dust-handling problems during manufacture.
Improved manufacturing/dosage form processing (e.g., for oils and low-melting-point drugs).
Often provide better dose uniformity for low-dose drugs.
Protection against oxidative degradation.
More costly than tablets, requiring specialized equipment.

Softgels Improve the BA

Softgel formulations increase absorption compared to tablets (e.g., ibuprofen, progesterone).

Formulation of Softgels Shells

Gelatin (40%), plasticizer (20-30%), and other materials for appearance and flavor.
Gelatin type B—important for high viscosity.
Plasticizers (e.g., glycerol, sorbitol, propylene glycol) improve elasticity for shell.
Water content—30-40% before encapsulation, typically 5-8% w/w in dry softgels.
API usually within the fill matrix.

Properties of Softgels Shells

Oxygen permeability—gelatin shell provides a barrier against oxygen diffusion (depending on glycerol content); higher glycerol content = lower permeability.
Residue water content—relatively low because of normal glycerol content.

Formulation of Softgel Fill Materials

Fill matrix selected based on physicochemical properties.
Criteria: dissolving capacity, dispersibility in GI tract, ability to remain dissolved, compatibility with shell, and optimized absorption rate/extend.

Types of Softgels Fill Matrices

Lipophilic liquids/oils (e.g., triglycerides, soya bean oil).
Hydrophilic liquids (e.g., polyethylene glycol, ethanol, water).
Self-emulsifying drug delivery systems (SEDDS) -combination of oil and surfactant for rapid emulsification/dispersion, generating micro/nanoemulsions for optimized absorption in GI tract.

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Description

This quiz focuses on the critical aspects of solid oral dosage forms, specifically hard and soft capsules. Learn about their components, properties, and formulation considerations essential for pharmacy students. Mastering these concepts is vital for successful drug formulation and patient care.