Eudragit (Ver12.0).pptx

Eudragit(Ver. 12.0)
Prepared Changbaek Lim
2023-07-10 1

Formulation Service
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The EUDRAGIT® advantage
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Unrivalled polymer versatility
to unlock the potential of your API
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Ideal for use with any oral solid dosage form
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Compatible with all relevant process technologies
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The functional flexibility to address
specific API and therapy requirements
Our poly(meth)acrylate copolymers feature physicochemical
properties that are determined by functional groups
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1. EUDRAGIT portfolio
2. Enteric formulation
3. Sustained-release formulations
4. Protective formulations
4.1 Taste masking
4.2 Moisture protection
5. Regulatory status and quality
6. Manufacturing of EUDRAGIT
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4.1 Taste masking
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EUDRAGIT portfolio I
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EUDRAGIT portfolio III
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Main structural skeleton of Eudragit polymers
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Different Eudragit grades, their chemical
composition, and physical properties
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Different Eudragit grades, their chemical
composition, and physical properties

EUDRAGIT portfolio IV
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pH-Dependent Release(G.I Trageting Formulation)

EUDRAGIT portfolio V
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pH-Independent Release(Sustained Release Formulation)

EUDRAGIT polymers for every application
EUDRAGIT portfolio II
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EUDRAGIT portfolio VI
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EUDRAGIT portfolio VII
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EUDRAGIT portfolio VIII
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Chemical structure of EUDRAGIT
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EUDRAGIT in coating applications
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EUDRAGIT as functional binder
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Predictable drug release site from dosage forms produced
with Eudragit polymers, according to their physicochemical properties

EUDRAGIT portfolio V
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 Eudragit RL과 RS는 아크릴과 메타크릴산 에스터로 공중합된 생체적합성 고분자
 Eudragit RL과 RS의 구조는 동일하나, 친수성인 4차 암모늄 치환체의 양이 서로 다름
 Eudragit RL : RS 보다 더 많은 4차 암모늄치환체를 가짐
☞Eudragit RL은 RS 보다 물에 대한 투과도가 높아 물을 더 잘 투과
 Eudragit RL과 RS는 물에 대한 투과도가 pH에 영향을 받지 않으며, 팽윤되지 않는 특성
☞ 아크릴-메타크릴 고분자들은 경구를 통한 타블렛과 펠렛의 반투막으로 주로 사용
☞ 물에 대한 불용성과 팽윤되지 않는 특성으로 인하여 약물의 방출을 쉽게 조절
☞서방형 제제의 약물 방출 제어기제로 널리 사용

4.1 Taste masking
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Products for enteric formulations
Functionality
Anionic polymers with methacrylic acid as a functional group and associated product
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Applications and advantages
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Chemical structure
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EUDRAGIT polymer properties
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EUDRAGIT Product forms
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EUDRAGIT L/S 100
: Example of an organic formulation for tablets
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EUDRAGIT L-30 D-55
: Enteric coating formulation for 100Kg tablets
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EUDRAGIT L-30 D-55
Enteric coating formulation for 100Kg tablets
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EUDRAGIT L-30 D-55
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EUDRAGIT L-30 D-55
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41
Drug Surface Calculations
and Determinations

Drug Surface Calculations and Determinations I
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 Since a certain layer thickness has to be achieved in film coating, the amount of
coating material is related to the surface area of the substrate
☞ It may be expressed in mg of dry polymer substance per cm² of surface area
 If we divide the surface area of a substrate A (mm2) by its weight w (mg),
we immediately obtain the requisite coating quantity in % (w/w),
i.e. the polymer quantity in kg of dry polymer substance per 100 kg of substrate
for a coating of 1 mg of dry polymer substance per cm2
 If lower or higher coating weights are specified for certain dosage forms, the
specific surface must be multiplied with this factor l (mg polymer per cm2)
 A : Surface area and l (mg/cm2) to the amount of film former
 Both quantities are linked by the factor 100, which leads to the result in percent
Calculation of polymer quantities

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 Depending on the desired function of a coating, the following values can be
used as orientation for the calculation of the required amount of polymer:
 Enteric coatings
 4 ~ 6 mg/cm² (Round Tablets)
 5 ~10 mg/cm² (Oblong-shaped Tablets)
 5 ~20 mg/cm² (Gelatin or HPMC Capsules)
 Taste-masking coatings
 1 – 2 mg/cm² (Round Tablets
 1 – 4 mg/cm² (Oblong-shaped Tablets)
 Moisture protection
 1 – 6 mg/cm² (Round Tablets
 2 – 10 mg/cm² (Oblong-shaped Tablets)
 5 – 10 mg/cm² (Gelatin or HPMC Capsules)
Drug Surface Calculations and Determinations II

Drug Surface Calculations and Determinations III
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Calculation of Surface Areas ; Simplified Calculations

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Drug Surface Calculations and Determinations IV
Calculation of Surface Areas ; Simplified Calculations

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Drug Surface Calculations and Determinations V
Calculation of Surface Areas ; Exact Calculations

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Shapes of Tablets

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Drug Surface Calculations and Determinations VI

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Drug Surface Calculations and Determinations VII

50
Drug Surface Calculations
and Determinations

Droplet size of water, atomized
with airborne sprays guns
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Influence of atomizing air pressure
on the quality of the coated film
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Influence of the water content
in organic coating formulations I
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Influence of the water content
in organic coating formulations II
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Influence of coating amount on enteric properties
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Influence of plasticizer : Eudragit L30 D-55
Minimum Filmforming Temperature (MFT)
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Influence of plasticizer on film quality
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Redispersion of Eudragit L 100-55
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K. Lehmann and H.-U. Petereit Pharm. Ind. 55, 6, 615 - 618 (1993)
Dissolution rate of Eudragit L /S films
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USP 25 , paddle apparatus
: 2h(pH 1.2)→1h(pH 5.0)→ 1h(pH 6.8)→1h(pH 7.5)
Stability data of enteric pellets
with colonic drug release
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Influence of EUDRAGIT type
on storage stability of enteric-coated crystals

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Colonic Drug Delivery
(Marketed Products)

Colonic drug delivery system
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Marketed Products
 Products marketed using DDS technology
 Entocort
 Asacol
 Pentasa
 Products by chemically modified
 Sulfasalazine
 Dipentum (olsalazine sodium)
 Colazal (balsalazide disodium)
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Formulation
250 mg
500 mg
acetylated monoglyceride, castor oil, colloidal silicon dioxide.
ethylcellulose, hydroxypropyl methylcellulose
starch, stearic acid, sugar, talc, and white wax
acetylated monoglyceride, castor oil, colloidal silicon dioxide.
ethylcellulose, hydroxypropyl methylcellulose
starch, stearic acid, sugar, talc, and white wax
Indication  Induction of remission and for the treatment of patients
with mildly to moderately active ulcerative colitis
Dosage Recommended dosage for induction of remission and symptomatic treatment of mildly to
moderately active ulcerative colitis : 1g
☞ 4 PENTASA 250 mg capsules or 2 PENTASA 500 mg capsules
4 times a day for a total daily dosage of 4g.
Treatment duration in controlled trials was up to 8 weeks
Pentasa Capsule
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Drug Layer
(Mesalazine)
Sustained Release Layer
( Ethyl cellulose )
 Controlled-Release Pellet (Hard capsule)
 Drug : Mesalazine 250 mg / 1 cap , Dosage : 4 cap(1g) /4 times /1day
 Indication : Ulcerative Colitis ( I.B.D ), Worldwide Launching
Pentasa Capsule
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Formulation Each tablet contains colloidal silicon dioxide, dibutyl phthalate, edible
black ink, iron oxide red, iron oxide yellow, lactose monohydrate, magnesium stearate,
methacrylic acid copolymer B (Eudragit S), polyethylene glycol, povidone, sodium
starch glycolate, and talc.
Indication Treatment of mildly to moderately active ulcerative colitis and for the maintenance of
remission of ulcerative colitis.
Dosage Treatment of mildly to moderately active ulcerative colitis
The usual dosage in adults is two 400-mg tablets to be taken three times a day for a total
daily dose of 2.4 grams for a duration of 6 weeks.
Maintenance of remission of ulcerative colitis
The recommended dosage in adults is 1 .6 grams daily, in divided doses
Treatment duration in the prospective, well-controlled trial was 6 months.
Two Asacol 400 mg tablets have not been shown to be bioequivalent to one Asacol HD
delayed-release 800 mg tablet
Asacol
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 pH-Controlled Colon Drug Delivery
 Drug : Mesalazine 400 mg /1 tablet
 Dosage : 2T/3 times /1day
 Indication : Ulcerative Colitis ( I.B.D )
 Leading Product among I.B.D Therapeutic Drugs
5-ASA
Uncoated Tablet
Coating Layer
(Eudragit–S)
pH ≥ 7.0
5-ASA
pH - dependent
Asacol
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Formulation
250 mg
500 mg
The LIALDA tablet contains 1.2 g mesalamine (5-aminosalicylic acid) in an MMX
Multi Matrix System core of hydrophilic and lipophilic excipients.
The MMX core is coated with a gastro-resistant film of methacrylic acid copolymers,
Type A , which delays mesalamine release until exposure to a pH of 6 respectively.
Upon disintegration of the coating, the core matrix forms a hydrogel and provides
extended release of mesalamine across the pH range of 6.8 to 7.2
The inactive ingredients of LIALDA tablets are sodium carboxymethylcellulose,
carnauba wax, stearic acid, silica (colloidal hydrated), sodium starch glycolate, talc,
magnesium stearate, methacrylic acid copolymer types A , triethylcitrate, titanium dioxide
red ferric oxide and polyethylene glycol 6000.
Indication  Induction of remission in patients with active, mild to moderate ulcerative colitis.
 Safety and effectiveness of LIALDA beyond 8 weeks has not been established.
Dosage The recommended dosage for the induction of remission in adult patients with
active, mild to moderate ulcerative colitis is two to four 1.2 g tablets to be taken
once daily with a meal for a total daily dose of 2.4 g or 4.8 g
Lialda
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Lialda
2정/1회/1일
4정/1회/1일
stearic acid
Carnauva wax
Sod. CMC
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Formulation of enteric coated
ASA crystals and tablets

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Elongation at break of EUDRAGIT film

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SEM photos of compressed film-coated particle

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Drug release of enteric coated
ASA crystals and tablets

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Storage stability of ASA crystals and tablets
12 % Eudragit L30D-55/NE30D=1:1

EUDRAGIT FS polymer
for colon delivery coating
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Products for enteric formulations
Functionality
Anionic polymers with methacrylic acid as a functional group and associated product
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Properties of EUDRAGIT FS30D
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EUDRAGIT FS30D
; Standard formulation
Example of a formulation for bisacodyl pellets
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EUDRAGIT FS 30 D
; highly flexible formulation
Example of a formulation fo r bisacodyl pellets / compression of coated particles
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EUDRAGIT FS30D
; influence of bed temperature
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EUDRAGIT FS30D
; influence of bed temperature
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Site specific drug release by combination of
EUDRAGIT FS30D & L30D-5 ( I )
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The mixing of EUDRAGIT® FS 30 D & L 30 D-55 can be used to adjust
the release of a dosage form in a range of pH 6.0 to pH 6.8

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Site specific drug release by combination of
EUDRAGIT FS30D & L30D-5 ( II )

Evonik solutions for enteric coatings
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Formulation Example EUDRAGIT® L 100-55
- redispersion to EUDRAGIT® L 30 D-55
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Formulation Example: EUDRAGIT® L 30 D-55
; Enteric coating with talc as anti-tacking agent
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Formulation Example : EUDRAGIT L30 D-55 + PlasAcryl
HTP20 as anti-tacking agent
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Enteric coating of hard gelatin capsules

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Enteric coating of hard gelatin capsules

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Uncoated hard gelatin capsule

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Enteric coated hard gelatin capsule

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Hard gelatin capsules coated with
Eudragit L30 D-55( Glidant : GMS)

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Case Study (ASA Tablet)

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Marketing requirements for a new product
56
56

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Development concept

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Review of drug stability

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Coating excipient compatibility test : Set-up

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Coating excipient compatibility test
: Effect of subcoat polymer

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: Effect of glidant

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: Effect of plasticizer

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: Effect of pigments

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: Conclusion

2. Enteric formulations
4.1 Taste masking
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Functionality
 Meth-/acrylate copolymers with trimethyl-ammonioethyl-methacrylate as a functional group
 Neutral polymer of meth-/acrylates
Sustained-release formulations
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 Applications:
 Sustained release formulations
 Suitable for matrix structures and miscible with other EUDRAGIT grades
 Advantages
 Time-controlled release of active ingredients
 Higher patient compliance due to reduced number of doses to be taken
 Cost-effective processing
 Suitable for matrix structures
 No plasticizer required, highly flexible
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Chemical structure I
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Chemical structure II
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Polymer properties
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Sustained-release formulation : Example I

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Sustained-release formulation : Example II

4.1 Taste masking
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Protective formulations
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Functionality
Cationic polymer with dimethyl-aminoethyl methacrylate as a functional group

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 Applications:
 Insulating coatings
 Taste masking
 Odor masking
 Moisture protection
 Light protection
 Bioavailability enhancement
 Advantages:
 Protection of sensitive actives
 Economical application
 Identification and incorporation of marketing attributes (color & gloss)
 Improved passage of the dosage form (smooth surface)
 Low viscosity, high pigment binding capacity, good adhesion, low
polymer weight gain

Chemical structure
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Polymer properties
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Taste masking formulation example I
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Aqueous colorless coating on Paracetamol granules
EUDRAGIT E PO, Paracetamol granules, Glatt WSG 2

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Dissolution test according USP 29 (apparatus 2)
100 rpm, 2 hours in 900 ml phosphate buffer pH 6.8
Taste masking formulation example II

Moisture protection formulation example
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Aqueous Colored Protective Coating on Tablets
in a Pan Coater EUDRAGIT E PO, Placebo Tablets

4.1 Taste masking
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Regulatory information
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Global Acceptance by international
registration authorities
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X = monograph (X) = draft submitted ( ) = planed
* DMF submitted prior 2010 and also containing safety data

Possible effects of EUDRAGIT
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4.1 Taste masking
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EUDRAGIT manufacturing process I
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EUDRAGIT manufacturing process II

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EUDRATEC Technology

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A strong track record of performance
across common formulation challenges

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Technology capabilities

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Particle manufacturing technologies
for formulation screening

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Extensive analytical capabilities

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Dissolution method capabilities

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EUDRA MOD
 EUDRA MOD I : Zero Order Drug Delivery
 EUDRA MOD II : Accerleated Drug Delivery
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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EUDRMOD I : Overview

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EUDRATEC MOD I : Proof of Concept

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EUDRATEC MOD I : Benefits

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EUDRA MOD
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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EUDRAMODE II : Overview

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EUDRATEC MOD II : Proof of Concept

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EUDRATEC MOD II : Benefits

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EUDRA MOD
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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EUDRPULSE : Overview

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EUDRPULSE : Proof of Concept

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EUDRPULSE : Benefits

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EUDRPULSE : Benefits

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EUDRA MOD
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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How Does EUDRACOL Work?
EUDRACOL is based on a multi-layer coating system providing drug protection
in the gastrointestinal tract and controlled drug release in the colon

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EUDRA MOD
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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EUDRATEC DuoCoat

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Review of drug stability

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DuoCoat mechanism
How does DuoCoatwork?

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DuoCoat approach: Case study

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Neutralization degree

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In vivo behavior of the DuoCoat technology
; Proof of concept in man

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Extension of the DuoCoat concept

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In vivo –Proof of concept

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Site of disintegration

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EUDRA MOD
EUDRA PULSE
EUDRA COL
EUDRA DUOCOAT
EUDRA PEP
EUDRATECH

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The EUDRATEC PEP
; Platform Technology

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Melt Extrusion Technology
using Eudragit Polymer

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Technology Overview

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Technology Overview I

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Technology Overview II

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Leistritz MICRO 18 GL 40 D Pharma & Extruder
Technology Overview III

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Technology Overview IV

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Technology Overview V

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Thermal Stability of EUDRAGIT Types
Technology Overview VI

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Equipment Overview I
Small Equipment for Feasibility Studies

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Equipment Overview II
Laboratory Scale Equipment for Strand Granulation

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Equipment Overview III
Laboratory Scale Equipment for Pellet Manufacture

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Technology Application

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Advantages Using EUDRAGIT in Melt Extrusion

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Glass Transition Temperatures and
Thermo Stability of EUDRAGIT Polymers

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Viscosity – An Important Parameter for
Melt Application of EUDRAGIT Polymers

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Requirements and Recommendations
Extrusion Equipment
 Our extruder is a twin-screw extruder, co-rotating and devided in several barrels
which also defi ne several temperature zones
 Some of the barrels have openings for feeding in Granules, powders or liquids e.g.
dispersions or solutions
 The opening can also be used for a venting or degassing step if necessary
 The screws of the extruder is segmented giving a high flexibility in defining the
screw-design as it is required for the extrusion run
 From conveying only property to a very high shear force applying screws is
everything possible
 The doser should work gravimetrically
 Separate Dosers for each component gives a better fl exibility in the daily R&D
work
 The air-cooled hot phase cutting Micropelletizer and the Strand Pelletizer are just
two of many possibilities for extruders to obtain a semi-finished dosage form.

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Taste Masking : Overview

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Taste Masking : Process

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Taste Masking : Example 1

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Taste Masking : Example I

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 Verapamil•HCl and EUDRAGIT L 100-55 do not show salt formation in IR spectroscopy but
still have good taste-masking properties with a tenfold reduction of the bitterness value
 Computational chemistry calculates the energetically stable form of Verapamil to the
hydrochloride salt, but shows bond distances to the functional groups of the polymer in the
typical range of Hbridge bonds
 These interactions were proved by detecting a partial protonation of the amino function of
verapamil by means of XPS (X-ray photoelectron spectroscopy), a method where soft X-ray
beams sputter out electrons from the sample surface
 Interaction also takes place during dissolution testing, enabling us to observe a sustained-
release profile at the pH of gastric fluid and of the intestine
Taste Masking : Example II

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Taste Masking : Example II

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Solubility Enhancement
 Together with permeability, the solubility of actives is a major factor for
oral bioavailability
 As the number of poorly soluble drugs has risen sharply in recent years,
techniques for improving the solubility, and potentially, the bio-
availability have become increasingly important
 Melt extrusion technology represents an efficient pathway for increasing
the solubility of poorly soluble drugs
 In the drug the active forms a solid dispersion where the drug is
presented in an amorphous state and molecularly dispersed in the
carrier
 This leads to an increase in solubility, as no lattice energy has to be
overcome during dissolution
 The particle size is reduced to the molecular level and the carrier
increases the wetting of the drug

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Case Study ; Felodipine, a Poorly Soluble Neutral Drug Used as Model Drug
 All EUDRAGIT® grades showed good applicability for embedding the drug in an
amorphous state, whereas EUDRAGIT E provides the increase in solubility
 Dissolution trials were performed in 500 mL of simulated gastric fluid pH 1.2 and stirred
at 100 rpm
 Extrusion of Felodipine, EUDRAGIT E and EUDRAGIT NE
 As the initially high solubility leads to a supersaturated solution, the drug preci-pitates and
the drug concentration decreases
 This may cause bioavailability problems in vivo
 To avoid recrystallization, a second, water-insoluble polymer (EUDRAGIT NE) was added
to the extrusion process, thus enabling the active to be stabilized in solution
 Compared to the pure active, the manufacture of a solid dispersion of felodipine and
EUDRAGIT E (10:90 ratio) results in a 360-fold increase in solubility
 Owing to its neutral character, ionic interactions like those with anionic or cationic drugs
are not likely to occur
 The solubility-increasing effect is caused by the amorphous state of the active, the drug/
polymer ratio and the properties of the polymer

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 All extrudates were examined by DSC and X-ray diffraction
 No crystalline fraction was observed
 This indicates an amorphous state of the active in the polymer

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Sustained Release Pellets : Overview
 Microspheres produced by an air-cooled micro pelletizer combined with a melt extrusion
process are excellent for controlled-release dosage forms
 The main purpose of this section is to compare microspheres with milled strand granules
 Benefits of the Microspheres
 Use for direct compression
 Use in capsules
 Good flow
 Excellent size and shape uniformity
 Economical manufacturing

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Sustained Release Pellets : Process
 Melt extrusion was carried out using a MICRO 18 GL 40D Pharma twin-screw extruder
from Leistritz Extrusionstechnik GmbH/Germany
 The screws were corotated at a speed of 140 rpm; the temperature applied was between 80
°C and 160 °C, the throughput 0.7 kg/h
 The micro pelletizer (Leistritz LMP 18 PH) was equipped with one knife, the die plate
had 8 holes of 1mm diameter each
 The resulting microsphere size is about 1 mm
 The microspheres have two diameters, one (D1) determined by the diameter of the die
holes, the other one (D2) determined by the combination of throughput and rotation speed
of the cutting knife or knives
 The smoothness of the pellet surface is determined by the viscosity of melt during the
cutting process, the cooling speed, the excipients etc.
 Microspheres produced by an air-cooled micro pelletizer combined with a melt extrusion
process are excellent for controlled-release dosage forms
 The main purpose of this section is to compare microspheres with milled strand granules

2023-07-10 205
Sustained Release Pellets
: Result & Discussion
 Microspheres produced on an air-cooled hot-melt cutting device show a very narrow
particle size variation with a span width of <0.7
 This produces pellets with a smooth surface that are very suitable for controlled release

2023-07-10 206
 Milled Extrudates containing EUDRAGIT RS and/or RL and theophylline, shows three
main features
 A strong correlation of drug release to the particle size within the first few minutes
 An initially rapid drug release within the first few minutes, caused by the irregular surface
produced by milling, followed by sustained release with a lower dissolution rate
 A weak influence of theophylline content on dissolution rate, which increases at smaller
particle sizes
 Unmmilled Microspheres show the following features
 Diffusion-controlled dissolution rate without pronounced surface effects
 Dissolution becomes continuously slower, following logarithmic kinetics, indicating a
diffusion-controlled mechanism
 The main difference in dissolution behavior between milled strand granulate and micro
spheres is the dissolution is plotted against the square root of time
 The dissolution from milled strand granules shows the two phases of initial burst followed
by sustained release
 The dissolution from microspheres shows a continuous profile

2023-07-10 207

2023-07-10 208

2023-07-10 209

2023-07-10 210
별첨자료 I :
Pharmaceutica Sphere

2023-07-10 211
별첨자료 II : Sugar Sphere

2023-07-10 212
Commercially available starter spheres I

2023-07-10 213
Commercially available starter spheres II

2023-07-10 214
Commercially available starter spheres III

2023-07-10 215
Drug Layering I
Schematic illustration of drug layering process of the active
substance from solution/suspension and polymer coating

2023-07-10 216
Drug Layering II
Schematic illustration of dry powder layering of
starter core and polymer coating

2023-07-10 217
Schematic illustration of drug release
from enteric-coated pellets (medium: high pH)

2023-07-10 218
Type of Pharmaceutica Sphere

LEADING THE WORLD IN EXCIPIENTS JRS PHARMA
Capsule Filling with
JRS Pharma‘s
NON-PAREIL SEEDS
Sacchari spheri Ph.Eur.,
Sugar Spheres USP / NF

4 names for one dosage form:
Globuli
Pellets
Spheres
Non-Pareils
JRS Pharma‘s
NON-PAREIL SEEDS
Sacchari spheri Ph.Eur.,
Sugar Spheres USP / NF

Capsule Filling
With Powder With Non-Pareils
Functions as carrier for
controlled or sustained
release drug delivery
technologies
No active function
Sugar based
MCC based
Lets talk about this!

Tablets are cheap – why to use capsules filled
with spheres?
 High Content Uniformity
 Consistent and controlled drug release
 Multiple drug can be combined in one unit
 High drug stability
 Many different ways to coat the active
 Easy Manufacturing Process
 Risk of drug dumping is reduced

Easy Manufacturing Process:
Active + (...) + Solvent:
1. Coating of NON-PAREIL SEEDS with an Active Solution
2. Drying of the pellets
For Sustained Release Formulations:
1. Coating of the Active-Spheres with coating material, e.g.
HPMC Solution, in different thickness
2. Drying of the pellets
Single Units Cores in different sizes
Active in the same concentration
Film in different thickness

Multiple Units
core
active
film
Single Units
Body
Disintegration with
different
release profiles

Easy Manufacturing Process:

Sustained Release Systems
Film coating systems: Limits
Working with spheres
(multiple dosage):
No problem !
Working with tablets
(single unit):
High risk !

Benefits of sustained release formulations?
 Homogenous blood concentration levels due to
their consistent distribution in the GI-tract
 Improved patient compliance by reducing
dose frequency
 Therefore reduced side effects
 Resistance of API to stomach acid

Characteristics of NON-PAREIL SEEDS?
 specially designed spherical particles
of uniform diameter within different grades
 white, uniform granules
 Remainder is chiefly starch

Important properties of NON-PAREIL SEEDS
 Sweet taste
 Practically inert and odorless
 Not sensitive against heat (up to 30°C)
 High breaking hardness – uniform surface
 Nearly no abrasion –
no dust development – therefore
easy to coat
 High surface area for the active coating

Monograph Specifications: Sugar Spheres NF
1. Appearance White, hard, brittle, free-flowing, spherical masses
2. Identification The insoluble portion of a slurry gives a reddish-violet
to deep blue color with iodine
3. Specific rotation + 41° - + 61°
4. Loss on drying not more than 4.0 %
5. Sucrose 62.5 – 91.5 % on dried basis
6. Residue on ignition not more than 0.25 %
7. Particle size (by RoTap)
not less than 90.0 % passes the coarser sieve
sieze stated in the labelling; 100 % passes the
next coarser sieve size listed in the labelling.
Not more than 10.0 % passes the finer sieve
size stated in the labeling.

U.S. Standard sieve sizes of NON-PAREIL SEEDS
Mesh µm
14 - 18 1000 - 1400
16 - 18 1000 - 1180
16 - 20 850 - 1180
18 - 20 850 - 1000
20 - 25 710 - 850
25 - 30 600 - 710
30 - 35 500 - 600
35 - 40 425 - 500
40 - 50 300 - 425
40 - 60 250 - 425

2023-07-10 231
별첨자료 II : Sugar Sphere

2023-07-10 232
Pharmasphere : Overview I
 Sugar spheres : a versatile excipient for oral pellet medications with modified release kinetics
 Sugar spheres are a widely used excipient for sustained-release pellet formulations

2023-07-10 233
Pelletization of active substances and sugar sphere coatings
Pharmasphere : Overview II

2023-07-10 234
Diagram to show the structure of a sustained release pellet
with sugar sphere (grey), active substance layer (red) and film coating (blue)
Pharmasphere : Overview III

Eudragit (Ver12.0).pptx

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