. I

!

Pharmaceutical Dosage Forms: Parenteral Medications Volume1 Second Edition, Revised and Expanded

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Motola and Agha!ormulation Research 163

g admixtures of d~ed good affinity of perilla ketone to Intralipid. This affinity should mini­• DSW, in both glr exposur: o~ drug to t~e pl~s~ic surfa~e . ~urthermore, the authors con­d at ambient temp~ed that dilution of the mtralip1d emulSion Wlth the formulated perilla ke­!Ompound is knowfl did not damage the emulsion and no physical changes were observed over !tion of time and ) 3 days. Based on this information, an admixture in Intralipid emulsion LVP fluid and col prepared and a simulated i. v . infusion test was conducted with PVC-,

.red is then recom: and PO-based i. v. sets. It was confirmed that there was no absorptive 3 of the drug to any of the i. v. sets tested.

simulated i. v. in lt • admixture in ;>repared as de- SUMMARY ' L VP container. lmixture is alloweis chapter presented various parameters that are considered important to 2 mJ /min. Samplrformulation research of parenteral products. With a good knowledge of usion period . Ttysical and organic chemistry and the techniques described, the preformu-monitored. The ion investigator can gather significant data to determine key properties of

3hou1d be recom-1ew compound and guide the formulator toward the next stage of product velopment.

ant loss of drug The following are typical preformulation worksheets that can be used to 1er investigation .mmarize all data during the progress of experiments.

a viable solutio1

i {S6J and is bri~EFORMULATION WORKSHEET cytotoxic agent~--------------------------------------------------------------

Compound Name or Designation:

Batch Number:

Molecular Weight:

Molecular Structure

'ehicle composed ls further dilutE :lated i. v. infu­eriment PVC-ion; Whereas, ;. Color: approXimately effluent sample! a. Description .n the first few ! as soon as b . APHA value in solution:

I Proposed to emulsion, e.g., :lt (log K) of ipid was meas-yrbean oil: water 6. Odor: /stems sug-

solvent:

wavelength:

Investigator(s):

Start Date:

I '1

Amneal Pharmaceuticals LLC – Exhibit 1026 – Page 163Petition for Inter Partes Review of US 8,455,527

228 DeLuca and Boylan

• ......-

Figure 30 Representative parenteral closures .

standardized alkalinity test run on powdered (ground) samples. Types II and III glass are soda lime, with type II being surface treated with sulfate, sulfite, or sulfide to make it less reactive . Type I glass is, theoretically, the best all- purpose glass for injectables and should be the only glass that is used with alkaline products . However, it is significantly more expensive than types II and III. Type II glass is often used for solutions that remain below pH 7. 0 during their shelf life, while type III glass can be used for dry pow­ders that are reconstituted. The particular glass container intended for use must be an integral part of the product stability program to be described later.

Unfortunately, specifying the type of glass is not sufficient to ensure the consistency needed. Manufacturers have different recipes that bear designa­tions , such as N-514A, CA-2, KG-33, and KG-35. Table 15 lists the compo­sitions of various glasses . The glasses vary in additives- such as oxides of boron, sodium , potassium, calcium, iron , and magnesium- which alter physi­cal and chemical properties of the glass . For example, when formulating sul­fate salts (e.g. , drug substances or antioxidant) , the glass container should have minimal amounts of calcium and barium to prevent the formation of insolu­ble inorganic sulfates [ 43]. To meet t his requirement KG- 33 type I should be specified.

Amber glass containers are often used where the product is suspected of being light sensitive. The amber color is imparted by the addition of iron and manganese oxides, the cations of which are known to catalyze oxidative reactions. Studies have shown that these ions are extracted from glass [72] and that the decomposition rate of several drugs, thiomerosal [ 73], amitripty­lene [74] , and L- ascorbic acid [75] is enhanced in amber glass containers.

The Parenteral Drug Association has published guidelines on the process­ing and selection of glass containers [76] . Various surface treatments are

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9 Glass Containers for Parenterals

R. Paul Abendroth

Kimble Glass, Inc., VIneland, New Jer·sey

Robert N. Clark

Owens- Brockway, Toledo, Onto

I. INTRODUCTION

This chapter discusses the nature of glass, the pharmacopeial classll'lcatlon of glass types, the varieties of glass containers used for parenteral packaging, the manufacture of glass containers, and their chemical and mechanical per­formance.

Containers made of glass provide the menufacturet:s of,parenterlll products w1th a nulll'bell of.j:lurable characteristiC§, >nclu_ding the Jollowing:

Ttiey ave good to excellent resist~!') to chemical 'nteruction with the contents.

2. They urc impermeable. With roQ_er closure, the lnte[!j_ty of the c'On-tuincd product is mah1tained.

3. They are easily cleaned in preparation for filling. 4. They are transparent, fucilitaling inspection of the contents. 5. They are rigid, strong, and dimensionally stable, and they can be

sterilized by any currently acceptable process. 6. They can be made An Integral t of medical devices for the admln-

istr · n of mcdlcatlon.

II. THE NATURE OF CLASS

Olass Is an Inorganic product of fusion that has cooled to a rigid condition without crystallizing. Glasses of commerce can have a very wide range of physlco.l nnd chemical properties, depending on tihe end use . Since the chem­ical and physical properties of glllBe depend on glass composition, the compo­sition of commercial glasses '!aries widoly.

361

II

" ..

Amneal Pharmaceuticals LLC – Exhibit 1026 – Page 361Petition for Inter Partes Review of US 8,455,527

Tab

le 1 R

epresen

tative C

on

tainer C

lass Com

po!rltlons

C"l

So

da-lim

e; T

yp

e II, III, or N

P B

oro

slllcate

, Ty

pe I

S' .. ..

Blow

n B

lown

Tu

bin

g

(') 0 ;3

~

Weight

(%)

Flint

Am

ber

Tu

bi.n

g flin

t F

lint

Am

ber

Flin

t F

lint

Am

ber

9. ;, ..

Si0

2 7

3.0

7

1.9

67

.7 6

7.8

66

.7 8

0.4

7

2.0

6

9.2

.. ..

B2

03

-

-1

.5

13

.6

9.5

1

2.9

1

1.4

1

0.4

Al2

03

1

.8

1.9

2

.8

5.8

5

.3

2.6

6

.8

5.4

CaO

10.7

10

.6

5.7

1

.1 1

.8

<0. OS 0

.5

0.4

MgO

0

.4

0.8

3.9

<

0.1

<

0.1 <0

.05

0

.2

0.3

BaO

-

-2

.0

2.4

1

.2

--

2.1

Na2 o

13.5

14

.1

15.6

8.3

7

.4

4.0

6

.1

6. 0

K2 0

0. 3 0

.3

0.6

0

.8

1.0

-

2.5

2

.3

Ti0

2 0

.02

0.0

4

--

--

-2

.8

Fe2 o

3 0

.04

0

.1

0.0

5

0.0

5

1.3

0

.06

0

.06

1

.0

FeO

0

.01

0.2

MnO

-

--

-6

.0

50

3

0.2 0

.01

0

.2

s2-

-0

.02

Cl-

--

-0

.2

0.3

0

.05 0

.1

0.2

Th

ermal ex

pan

sivit-ya

88 90

93 56

59 32

55 54

Po

wd

ered g

lass testb

7

.0

7.6 8

.0

0.6

0

. 7 0

.3

0.3 0

.4

8Th

ermal ex

pan

slvity

Ia giv

en as u

nits o

f len

gth

per 1

0,0

00

,00

0 u

nits p

er °C

for th

e ran

ge from

0 to

300°C.

~

"" b

Po

wd

ered g

lass teat v

alues a

rc g

iven

as millilite

rs 0. 02 N H

2 so4 .

--.. --

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