Vortrag ExcipientFest2017

Sugar Spheres: Improving clinical
effectiveness with multiparticulate drug

delivery systems
Philipp Werner
www.pharm-a-spheres.com
Introduction
sugar sphere as core
Active
ingredients
coated on the
sugar spheres
controlled-release
coating and finishing
Pharmaceutical product portfolio
Standard and
custom sized
Micropellets
sugar spheres
(EP and USP/ NF)
Globuli sacchari
xylitol and
lactose globuli
nutritional
supplements
Introduction
What are multiparticulate oral dosage forms?
Types of pellets
Sugar spheres and their benefits
Multiparticulates improve clinical effectiveness?
Technological benefits of multiparticulates
Focus: Modified release formulations
Mechanisms of coating
Multiparticulate drug delivery systems
Multiparticulate drug delivery systems are mainly oral dosage forms

consisting of a multiplicity of small discrete units, each exhibiting some
desired characteristics.
Pellets Microtablets
Which types of pellets are there?
Matrix Pellets Coated starter core
By extrusion, granulation or By coating of an already existing

spheronisation. starter core
Both kind of pellets will normally be finished by at least one coating
Starter cores - Requirements
High patient compatibility Technologically suitable
Easy digestible Good coating properties

No side effects High yield (low friability)
No Microbial contamination Uniformity of particle size
Easy to use
In compliance!
In respect to EP & USP
Starter cores - sugar spheres
High patient compatibility
Easy digestible
No side effects
No Microbial contamination
Only sugar & corn starch

All natural
Digestible
Biodegradable
Outstanding microbial
Quality
High degree of sphericity

Smooth surface
Technologically suitable
Chemically indifferent excipients
No incompatibilites Good coating properties
High yield (low friability)
High mechanical stability Uniformity of particle size
No attrition Easy to use
Low friability
USP/NF: sugar spheres EP: 1570 sugar spheres
In compliance!
In respect to EP & USP
Improving clinical effectiveness
Why use multiparticulate drug delivery systems?
Subsequently drawn from the stomach
The effect of food on gastrointestinal tract is

minimized
Greater and more reproducible dispersion

throughout the gastrointestinal tract can be
achieved.
Improving clinical effectiveness
Why use multiparticulate drug delivery systems?
Greater and more reproducible dispersion

throughout the gastrointestinal tract can be
achieved.
The risk of local The risk of dose

toxicity decreases dumping is strongly
decreased due to mutual
redundance of a single
unit
Easy coating at a constant Stable mixtures - Easy

thickness assembly
Highly controllable Easy dose adjusting
Low stress on API (coating) Simultaneous release of

incompatible APIs
The single most important factor responsible for the

proliferation of pelletized products is the popularity of
controlled release technology in the delivery of drugs
Potentially any release profile
Potentially several APIs
Several ways of achieving

modified release
The term modified release is used to identify drug delivery systems that are
designed to achieve or extend therapeutic effect by continuously releasing
medication over an extended period of time after administration of a single
dose.
As long Where it
as it is is
required required
When it is
required
Drug
plasma
level
Immediate release profile
Time
Drug
plasma
level
sustained release profile
Time
Drug
plasma
level
delayed release profile
Time
pulsed release profile

Drug
plasma
level
Time
Drug
plasma
level
Intestinal release profile
pH=1,2 pH=8,4
Time
How to control the release?
Mechanisms of membrane controled drug release
Diffusion Osmosis Erosion
Control drug release by: Diffusion
Building a Diffusion-
saturated controlled
reservoir release
Membrane permeable for surrounding medium and API
API decreases if concentration is lower than saturation
Control drug release by: Osmosis
Building an osmosis-
osmotic controlled
gradient release
Membrane permeable for surrounding medium, NOT for API
API decreases if osmotic pressure decreases with API concentration
Control drug release by: Erosion
Erosion of
outer layer
Outer layer is soluble in the surrounding medium
API is released after erosion of the outer layer
Controlling point of release by Erosion
Stomach Sustained release layer

pH ~1.2
Starter core
Intestine
pH ~8.4
API
Colon
azoreductases pH-dependant erosion layer
Controlling release profiles by heterogeneous mixtures of multiparticulates
Heterogeneous Multiparticulates
Same API - Different release profiles Different API - several release profiles
Multiparticulates with different release profiles can easily be assembled in

one capsule
Even different APIs with different release profiles can be combined this way
Coating basics
Powder layering
Solid bridge
Liquid bridge
Adhesion
First layer
Coating basics
Suspension layering
Spreading
First layer
Crystallization
Spraying
Coating basics
Depending on the required properties of the pellet several coating processes

are possible. The most popular are pan coating and fluid bed coating.
Pan coater Fluidized bed coater
Summary
Multiparticulate drug delivery Pellet based systems either

systems are mainly oral consist of matrix pellets or
dosage forms consisting of a coated starter cores. For
multiplicity of small discrete several reasons sugar
units, each exhibiting some spheres spheres are widely
desired characteristics. used as starter cores.
Summary
Due to their small size and The single most important

multiple redundance factor responsible for the
multiparticulates can greatly proliferation of pelletized
improve clinical effectiveness products is the popularity of
and safety of pharmaceutical controlled release technology
formulations in the delivery of drugs
Summary
There are different ways to Heterogeneous

achieve membrane controlled multiparticulate dosage forms
drug release. Most important can be utilized to easily
mechanisms are: Diffusion, achieve complex release
osmosis and erosion profiles of one or several APIs
Summary
Basic mechanisms of coating Widely used processes in

are powder coating and manufacturing coated
suspension layering. Whicht o multiparticulate oral dosage
use depends on the required forms are pan coating or
properties and especially the fluidized bed technology
anticipated API-load

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Sugar Spheres: Improving clinical

effectiveness with multiparticulate drug

sugar sphere as core

What are multiparticulate oral dosage forms?

Multiparticulates improve clinical effectiveness?

Technological benefits of multiparticulates

Focus: Modified release formulations

Multiparticulate drug delivery systems are mainly oral dosage forms

Matrix Pellets Coated starter core

By extrusion, granulation or By coating of an already existing

Both kind of pellets will normally be finished by at least one coating

High patient compatibility Technologically suitable

Easy digestible Good coating properties

In respect to EP & USP

High patient compatibility

Only sugar & corn starch

High degree of sphericity

USP/NF: sugar spheres EP: 1570 sugar spheres

In respect to EP & USP

Why use multiparticulate drug delivery systems?

Subsequently drawn from the stomach

The effect of food on gastrointestinal tract is

Greater and more reproducible dispersion

Why use multiparticulate drug delivery systems?

Greater and more reproducible dispersion

The risk of local The risk of dose

Easy coating at a constant Stable mixtures - Easy

Highly controllable Easy dose adjusting

Low stress on API (coating) Simultaneous release of

The single most important factor responsible for the

Potentially any release profile

Potentially several APIs

Several ways of achieving

pulsed release profile

Mechanisms of membrane controled drug release

Diffusion Osmosis Erosion

Control drug release by: Diffusion

Membrane permeable for surrounding medium and API

API decreases if concentration is lower than saturation

Control drug release by: Osmosis

Membrane permeable for surrounding medium, NOT for API

API decreases if osmotic pressure decreases with API concentration

Control drug release by: Erosion

Outer layer is soluble in the surrounding medium

API is released after erosion of the outer layer

Controlling point of release by Erosion

Stomach Sustained release layer

Controlling release profiles by heterogeneous mixtures of multiparticulates

Multiparticulates with different release profiles can easily be assembled in

Depending on the required properties of the pellet several coating processes

Pan coater Fluidized bed coater

Multiparticulate drug delivery Pellet based systems either

Due to their small size and The single most important

There are different ways to Heterogeneous

Basic mechanisms of coating Widely used processes in

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