hydroxypropyl methyl cellulose (hpmc)

www.wjpps.com Vol 3, Issue 9, 2014.

551

Phadtare et al. World Journal of Pharmacy and Pharmaceutical Sciences

HYPROMELLOSE – A CHOICE OF POLYMER IN EXTENDED

RELEASE TABLET FORMULATION

Dipti Phadtare*, Ganesh Phadtare , Nilesh B*, Mahendra Asawat*

* Pacific Academy for Higher Education and Research, Faculty of Pharmacy, Udaipur, India.

ABSTRACT

Hydroxypropylmethylcellulose (HPMC) also know as hypromellose, is

largely in used cellulose ether in the development of hydrophilic

matrices. Hypromellose provides the release of a drug in a controlled

manner, effectively increasing the duration of release of a drug to

prolong its therapeutic effect. This review provides a current insight

into hypromellose and its applicability to hydrophilic matrices in order

to highlight the basic parameters that affect its performance. Topics

covered include the chemical, thermal and mechanical properties of

hypromellose, hydration of the polymer matrices, the mechanism of

drug release and the various models used to predict the kinetics and

mechanism of drug release from the HPMC matrices. This review also provides the

maximum potency of hypromellose used in various dosage form and current patent status

review of hypromellose as a release controlling polymer in extended release matrix systems.

Keywords: Hydrophilic matrix; HPMC; release mechanism; mathematical models; patent

Hydroxypropyl methylcellulose ethers belong to an extensive family of white to off-white,

odorless, water soluble polymers that bind, retain water, thicken, form films, lubricate, and

much more. Synonym for hydroxypropyl methylcellulose (HPMC) is Hypromellose. It is a

semi synthetic, inert, viscoelastic polymer, used as an excipient and controlled-delivery

component in oral medicaments, found in a variety of commercial products.

Hypromellose is a methylcellulose modified with a small amount of propylene glycol ether

groups attached to the anhydroglucose of the cellulose. It is a methyl and hydroxypropyl

mixed ether of cellulose. The product contains, calculated on dry basis, 19 % to 30 % of

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SSJJIIFF IImmppaacctt FFaaccttoorr 22..778866

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Article Received on

25 June 2014,

Revised on 20 July

2014,

Accepted on 13 August 2014

*Correspondence for Author

Dipti Phadtare

Pacific Academy for Higher

Education and Research,

Faculty of Pharmacy, Udaipur,

India.


552


methoxyl (-OCH3) groups and 3 % to 12 % of hydroxypropyl (-OCH2CHOHCH3) groups.

The limits for the types of Hypromellose (hydroxypropyl methylcellulose) set forth in the

table 1. [1-2]

Table 1

Substitution Type Methoxy (%) Hydroxypropyl (%)

Minimum Maximum Minimum Maximum

1828 16.5 20.0 23.0 32.0

2208 19.0 24.0 4.0 12.0

2906 27.0 30.0 4.0 7.5

2910 28.0 30.0 7.0 12.0

Table 2: The critical attributes of Hypremellose described in some of pharmacopoeias

are listed in below table.

Attribute JP EP USP

Definition + + +

Labeling + + +

Identification (A) + + +

Identification (B) + + +

Identification (C) + + +

Identification (D) + + +

Identification (E) + + +

Viscosity, Method 1 + + +

Viscosity, Method 2 + + +

Attribute JP EP USP

pH + + +

Heavy Metals + + +

Loss on Drying + + +

Residue on Ignition + + +

Assay + + +

Legend: + will adopt and implement; will not stipulate

Nonharmonized attributes: Packaging and Storage

Specific local attributes: Appearance of solution (EP), Description (JP), Limit of glyoxal

(EP) [2]

Chemistry

Hypremellose have the polymeric backbone of cellulose, a natural carbohydrate that contains

a basic repeating structure of anhydroglucose units (See figure below). During the

manufacture of cellulose ethers, cellulose fibers are heated with a caustic solution which in

turn is treated with propylene oxide, yielding hydroxypropyl substitution on the


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anhydroglucose units of methyl ether of cellulose. The fibrous reaction product is purified

and ground to a fine, uniform powder.

Fig. 1. Chemical structure of HPMC.

The substituent R represents either a –CH3, or a –CH2CH(CH3)OH group, or a hydrogen

atom.

Hypromellose possess varying ratios of Hydroxypropyl and Methyl substitution which in

turns determine the organic solubility as well as thermal gelation temperature of aqueous

solution. The extent of substitution is designated by weight percentage of substituent group

attached to the ring; know as „degree of substitution‟ (D.S.). A lower D.S. results in lower

solubility and is only soluble in caustic solution. The letter „E‟, „K‟, „J‟ and „F‟ identify the

different Hypromellose grade product with respect to their properties. The suffix „S‟ denotes

„surface treated, „G‟ denotes „Granular grade‟ while „CR‟ denotes „Controlled Release‟

grade. In „E‟, „F‟ and „K‟ grade products the substitution is major constituents as mentioned

in below table while in case of „J‟ it is about 50% of the total substitution.[1]

Table 3: Degree of Substitution for different grades of Hypromellose

Grade Methoxyl D.S. Methoxyl % Hydroxypropyl Molar

Substitution

Hydroxypropyl

%

E 1.9 29 0.23 8.5

K 1.4 22 0.21 8.1

F 1.8 28 0.13 5.0

J 1.3 18 0.82 27


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Properties

General properties common to the Hypremellose are listed below. Individual type exhibits

these properties to varying degrees and may have additional properties that are desirable for

specific applications.

1) Apparent density: 0.25~0.70g/cm 3 (Typical:0.5g/cm 3 );

2) The refractive index of 2% aqueous solutions at 20°C is for all types: nD20

=1.336

3) For Hypromellose powders, the following values are used

a. Specific heat, Cp = 0.28 BTU/lb-F

b.Thermal conductivity, k = 0.028 BTU/hr-ft-F

4) Approximate values for specific gravity are given for some concentration below

a. 1% solution: 1.0012

b.5% solution: 1.0117

c. 10% soluton: 1.0245

5) Surface tension: Surface tensions range from 42 to 56 mN/m. The surface tension of water

is 72 mN/m; a typical surfactant has a surface tension of 30 mN/m.

6) Dissolubility: dissolve in water and some solvent. Such as, the suitable proportion of

ethanol/ water, propanol /water. Its aqueous solution provides surface activity and high

transparence and stable properties. Various products have different gel temperatures.

Solubility changes with viscosity. Lower the viscosity is, higher the solubility is. Different

types of Hypremellose have different properties. Its dissolution is not subject to pH.

7) With the reduction of methoxy content, gel point rises, solubility in water and surface

activity decrease.

The most critical property of Hypromellose is a viscosity. The viscosity of an aqueous

solution of a Hypromellose is proportional to the molecular weight or chain length of the

specific Hypromellose product used. Commercial designations of Hypromellose products are

based on viscosity values determined in water at 20°C, with a concentration of 2%

Hypromellose. The table below provides further information regarding the commercial

viscosity designation. All the products mentioned in table are Premium EP grades, which

means they meet the compendial requirements of the US and European Pharmacopoeias.


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*CR – Controlled Release Grades

** LH - Product with lower Hydroxypropyl content specification 7%-9%

Table 4: Hypromellose Commercial grade with respective viscosity

USP Designation Hypromellose Commercial grade Viscosity (cP)

2910 E 3 Premium LV 3





2910 E 4M Premium 4000

2910 E 4M Premium CR 4000

2910 E 10M Premium CR 10000

2906 F 4M Premium 4000

2208 K 3 Premium LV 3

2208 K 100 Premium LV 100

2208 K 100 Premium LV CR* 100

2208 K 100 Premium LV LH** 100

2208 K 100 Premium LV LH CR 100

2208 K 4M Premium 4000

2208 K 4M Premium CR 4000

2208 K 15M Premium 15000

2208 K 15M Premium CR 15000

2208 K 100M Premium 100000

2208 K 100M Premium CR 100000

Hypromellose Dissolving Methods

1) Product with surface treatment(s) can be added in tap water directly and can disperse

quickly through agitating. The solution pH value can be adjusted to the range of 8-9 by

adding in alkali in form of ammonia and Na2CO3. By agitating the solution viscosity can be

increased.

2) Product without surface treatment can swell and disperse in hot water with temperature

higher than 85ºC. Usually it is dissolved by the following methods. Take about 1/5~1/3 of the

needed hot water and agitate so that the added product will swell completely. Then add in the

remained water, which can be hot or cold, agitate to the appropriate temperature and the

product can dissolve completely. As to dissolve HPMC by hot water method, it is very

important to cool the mixture down. To dissolve the product completely and form ideal

transparent solution, the temperature is dependant upon the type of HPMC.


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3) Dispersing by dry mixing, i.e., the product can be mixed with other powder substance

homogeneously first, and then tap water is added in, so that the product will dissolve quickly

without any gel.

4) Wetting with organic solvent. Disperse the product in organic solvent first or wet the

product by organic solvent and then add the mixture into hot water or add in hot water, which

could also dissolve the product efficiently. The organic solvent could be ethanol or ethandiol

[3].

GRAS status

Based on the information provided by Dow, as well as other information available to FDA,

the agency has no questions at this time regarding Dow's conclusion that HPMC-ESP is

GRAS under the intended conditions of use. The agency has not, however, made its own

determination regarding the GRAS status of the subject use of this ingredient. As always, it is

the continuing responsibility of Dow to ensure that food ingredients that the firm markets are

safe, and are otherwise in compliance with all applicable legal and regulatory requirements.

In accordance with proposed 21 CFR 170.36(f), a copy of the text of this letter responding to

GRN 000213, as well as a copy of the information in this notice that conforms to the

information in the proposed GRAS exemption claim (proposed 21 CFR 170.36(c)(1)), is

available for public review and copying on the homepage of the Office of Food Additive

Safety. http://www.cfsan.fda.gov/~lrd/foodadd.html

Pursuant to proposed 21 C.F.R. 5 170.36(c), on the basis of scientific procedures in

accordance with 21 C.F.R. 5 170.30, that the use of its hydroxypropyl methylcellulose

(HPMC) product is generally recognized as safe (GRAS) when used in food for multiple

technical effects, including as a source of dietary fiber. The enclosed Notification is a revised

version of the GRAS Notice that was submitted by Dow Chemical. The Food and Drug

Administration (FDA) is responding to the notice, dated September 20, 2006, that you

submitted on behalf of the Dow Chemical Company (Dow) in accordance with the agency's

proposed regulation, proposed 21 CFR 170.36 (62 FR 18938; April 17, 1997; Substances

Generally Recognized as Safe (GRAS); the GRAS proposal). FDA received the notice on

September 22, 2006, filed it on September 27, 2006, and designated it as GRAS Notice No.

GRN 000213.

http://www.cfsan.fda.gov/~lrd/foodadd.html


557


The subject of the notice is hypromellose, a propylene glycol ether of methylcellulose

containing 16-31.5 percent methyl groups and 2-32 percent hydroxypropyl groups. For the

purpose of this letter, FDA refers to the subject of the notice as "HPMC - expanded

substitution pattern" (HPMC-ESP). The notice informs FDA of the view of Dow that HPMC-

ESP is GRAS, through scientific procedures, for use in food in general, including meat and

poultry products, at intake levels up to 20 grams per person per day (g/p/d). The detail

information of GRAS status of hypremellose is uploaded on the link below

http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GR

ASListings/ucm153856.htm

Inactive Ingredient Database

According to 21 CFR 210.3(b)(8), an inactive ingredient is any component of a drug product

other than the active ingredient. Only inactive ingredients in the final dosage forms of drug

products are in this database.

The Inactive Ingredients Database provides information on inactive ingredients present in

FDA-approved drug products. This information can be used by industry as an aid in

developing drug products. For new drug development purposes, once an inactive ingredient

has appeared in an approved drug product for a particular route of administration, the inactive

ingredient is not considered new and may require a less extensive review the next time it is

included in a new drug product.

Hypromelose is also included in the inactive ingredient database. Following table depict

some of the approved drug product in which it is used as a inactive ingredient with its route

of administration and maximum potency. [4-5] The table mainly summarizes the use of

Hypromelose as release retarding inactive ingredient. For other applications, information is

provided on the link below.

1. http://www.accessdata.fda.gov/scripts/cder/iig/getiigWEB.cfm

2. http://www.fda.gov/Drugs/InformationOnDrugs/ucm075230.htm)

3. http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelo

pedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationAND

http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASListings/ucm153856.htm

http://www.fda.gov/Food/FoodIngredientsPackaging/GenerallyRecognizedasSafeGRAS/GRASListings/ucm153856.htm

http://www.accessdata.fda.gov/scripts/cder/iig/getiigWEB.cfm

http://www.fda.gov/Drugs/InformationOnDrugs/ucm075230.htm

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationAND

http://www.fda.gov/downloads/Drugs/DevelopmentApprovalProcess/HowDrugsareDevelopedandApproved/ApprovalApplications/AbbreviatedNewDrugApplicationAND


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Table 5:

Inactive Ingredient Route;Dosage form UNII Maximum

Potency

HYPROMELLOSE

2208 (15000 MPA.S)

ORAL; CAPSULE, SUSTAINED ACTION Z78RG6M2N2 336MG

ORAL; CAPSULE, SUSTAINED ACTION, HARD

GELATIN Z78RG6M2N2 2.771MG

ORAL; TABLET Z78RG6M2N2 86MG

ORAL; TABLET, CONTROLLED RELEASE Z78RG6M2N2 7.8MG

ORAL; TABLET, EXTENDED RELEASE Z78RG6M2N2 320MG

ORAL; TABLET, SUSTAINED ACTION Z78RG6M2N2 480MG

ORAL; TABLET, SUSTAINED ACTION,

COATED Z78RG6M2N2 94MG

ORAL; TABLET, SUSTAINED ACTION, FILM

COATED Z78RG6M2N2 200MG

HYPROMELLOSE

2208 (60000 MPA.S) ORAL; TABLET, EXTENDED RELEASE 2F7T07H9ZD 175MG

HYPROMELLOSE

2208 (80000-120000

CPS)

ORAL; TABLET, EXTENDED RELEASE VM7F0B23ZI 54MG

HYPROMELLOSE

2910 (15000 MPA.S)

ORAL; CAPSULE, DELAYED ACTION 288VBX44JC 33.42MG

ORAL; CAPSULE, ENTERIC COATED PELLETS 288VBX44JC 13.82MG

ORAL; CAPSULE, EXTENDED RELEASE 288VBX44JC 10.6MG

ORAL; CAPSULE, SUSTAINED ACTION 288VBX44JC 10.88MG

ORAL; CAPSULE, SUSTAINED ACTION, HARD

GELATIN 288VBX44JC 4.772MG

ORAL; TABLET, CONTROLLED RELEASE 288VBX44JC 20MG

ORAL; TABLET, DELAYED ACTION 288VBX44JC 4.47MG

ORAL; TABLET, DELAYED ACTION, ENTERIC

COATED 288VBX44JC 19MG

ORAL; TABLET, ENTERIC COATED

PARTICLES 288VBX44JC 445MG

ORAL; TABLET, EXTENDED RELEASE 288VBX44JC 150MG

ORAL; TABLET, ORALLY DISINTEGRATING,

DELAYED RELEASE 288VBX44JC 7MG

ORAL; TABLET, SUSTAINED ACTION 288VBX44JC 250MG

ORAL; TABLET, SUSTAINED ACTION,


ORAL; TABLET, SUSTAINED ACTION, FILM


HYPROMELLOSE

2910 (4000 MPA.S) ORAL; CAPSULE, EXTENDED RELEASE 27MG

HYPROMELLOSE

2910 (50 MPA.S) ORAL; CAPSULE, EXTENDED RELEASE 54MG

HYPROMELLOSE

2910 (6 MPA.S) ORAL; TABLET, EXTENDED RELEASE 0WZ8WG20P6 92.794MG







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Application

Hypromellose is a water-soluble polymer derived from cellulose, the most abundant polymer

in nature. It is used as thickener, binder, film former, and water-retention agent.

Hypromellose is also function as suspension aids, surfactants, lubricants, protective colloids

and emulsifiers. In addition, solutions of HPMC, thermally gel, a unique property that plays a

key role in a surprising variety of applications. Such a kind of valuable combination of

properties is not available in any other water-soluble polymer.

Hydroxypropyl methylcellulose Ethers are highly efficient, often yielding optimum

performance at a lower concentration than that required with other water-soluble

polymers.The broad range of Hydroxypropyl methylcellulose is certainly one reasonit is used

successfully in so many different applications. There are many different chemical types and

each is available in different grades, physical forms, and viscosities. Available viscosity

grades range from 3 to over 200,000 mPas.

Hydrophilic matrix systems designed with water-soluble polymers, such as Hypromellose,

were first introduced in the early 1970‟s. Since then, development work has concentrated on

controlled release technology, and many types of advanced polymers and techniques have

become available. The hydrophilic matrix system is the simplest sustained release technology

for oral dosage forms, consisting essentially of a drug and a water soluble, highly viscous

polymer. It does not require any other excipient. Recent advances in this hydrophilic matrix

system have allowed more controllable and reproducible drug release by controlling the

chemical and physical properties of the polymer. Hypromellose is especially suitable for this

application, and provides a genuine consistency in the final products.

Hydrophilic Matrices

The principle of drug release from hydrophilic polymers is due to hydration and swelling

(Figure 1) During the initial formation of the gel layer a preliminary burst of drug release is

typical. The extent of the burst is dependent on the solubility of the drug substance and how

rapidly the polymer can hydrate to form the gel layer, which is influenced by the polymer

chemistry and particle size. Reducing the particle size of the polymer reduces the burst

release and eventually slows down the rate of release (this is because the hydration rate of the

gel increases and gel layer forms more rapidly). Once the gel layer has formed, it controls

the release rate of the drug substance, principally by diffusion control for high solubility


560


drugs, erosion control for low solubility drugs or by a combination of diffusion and erosion.

The polymer viscosity controls the rate of erosion.

Initial Tablet

Figure 1 Drug Release from a Hydrophilic Matrix

The most commonly used polymers for hydrophilic matrices are Hydroxypropyl methyl

cellulose (Hypromellose or HPMC). Hydrophilic matrices based on HPMC are the most

common and have the widest application across a range of drug substance properties. When

formulating with HPMC, consideration needs to be given to the following factors, which

affect the dissolution profile

HPMC content

HPMC to drug ratio

HPMC viscosity

Drug solubility

HPMC substitution

HPMC particle size

Drug particle size

Diluent particle size

Diluent solubility

The above factors should be incorporated into a DOE to fully understand their effect in

controlling the dissolution rate of each compound. Detailed information regarding the use of

HPMC for controlled release of drugs in hydrophilic. Within each substitution type and

Gel layer

expands Water continue to permeate the

core and the hydrated outer layer dissolves

Water insoluble drug is released through

tablet erosion

Water soluble drug is released by

diffusion through the tablet core


561


viscosity, additional sub grades maybe available e.g. CR (tighter control on polymer particle

size) low humidity and low substitution, and these should be selected with care. [6]

It is possible to combine different polymer chemistry and viscosities to further control the

release profile. However, caution is recommended as this may result in a combination of

release mechanisms which may be difficult to interpret in-vitro or in-vivo.

Examples of suitable HPMC grades for modified release formulation development are listed

in Table 6

Table 6: HPMC Grades Suitable for Controlled Release

USP

Designation

Methocel Product Shinetsu Product Nominal Voscosity

cP1

2910 E4M Premium EP Metolose 60SH 4000

2910 E4M Premium CR EP - 4000

2910 N/A Metolose 60SH 10000

2910 E10M Premium CR

EP

- 10000

2208 K100 LV EP Metolose 90SH 100

2208 K4M Premium EP Metolose 90SH 4000

2208 K4M Premium CR EP Metolose SR 90SH 4000


2208 K15M Premium CR

EP

- 15000


2208 K100M Premium CR

EP

Metolose SR 90SH 100000

1. cP (cps) is equivalent to milli Pascal second

Matrix Tablet Formulations

Application Benefits

Typically Used

METHOCEL Cellulose

Ethers

Low Solubility Drugs Fast polymer hydration to

form gel layer; non-ionic

E50LV, K100LV, K100LV

CR

Med to High Solubility Drugs Fast polymer hydration to

form gel layer; non-ionic

K4M, K15M, K100M, E4M,

E10M, K4MCR, K15MCR,

K100MCR, E4MCR,

E10MCR

Release Mechanism

The overall drug release mechanism from HPMC based pharmaceutical devices strongly

depends on the design (composition and geometry) of the particular delivery system. Drug

molecules are released at the surface, as well as diffusing into the inner swelling polymer (a


562


dissolution process) and then diffusing outwards through the swelling polymer and finally

through the outer gel layers.

In the GIT HPMC matrix undergoes:

1) surface wetting (rapid)

2) surface swelling (slow process)

3) surface erosion (ongoing)

4) surface gel formation (ongoing)

5) gradual inner polymer swelling

6) ongoing outer gel erosion

Figure 2: Schematic illustration of a swellable hypromellose-based matrix during drug

release.

The three distinct moving fronts are indicated. At all times the dissolved drug profile extends

from the diffusion to the erosion front and the water profile from the swelling to the erosion

front (i.e. the entire gel layer).

At the beginning of the process, steep water concentration gradients are formed at the

polymer/ water interface resulting in water imbibition into the matrix. Water acts as a

plasticizer and reduces the glass transition temperature of the system; the polymer chains

undergo the transition from the glassy to the rubbery state. Due to the imbibition of water

HPMC swells, resulting in dramatic changes of polymer and drug concentrations, and

increasing dimensions of the system.

Diffusion front Swelling front

Erosion front


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Upon contact with water the drug dissolves and (due to concentration gradients) diffuses out

of the device. With increasing water content the diffusion coefficient of the drug increases

substantially.

In the case of poor water-solubility, dissolved and non-dissolved drug coexist within the

polymer matrix. Non-dissolved drug is not available for diffusion. In the case of high initial

drug loadings, the inner structure of the matrix changes significantly during drug release,

becoming more porous and less restrictive for diffusion upon drug depletion.

Depending on the chain length and degree of substitution of the HPMC type used, the

polymer itself dissolves more or less rapidly.

Active drug is released in the gastrointestinal tract via contributions from different release

mechanisms. Initially surface erosion of the tablet face occurs and water imbibes into the

polymer matrix. Slow direct erosions of the polymer matrix and erosion, after transient

swelling, at the surface with the formation of a gel layer occur. Diffusion release of the drug

from the polymeric matrix results, through the swelling gel layer, with concomitant ongoing

polymer surface erosion. At the end of the drug release, the matrix is completely dissolved,

suggesting that the overall drug release time is controlled by the tablet erosion. [8-11]

Kinetics of Drug Release

In order to understand the mechanism and kinetics of drug release from hypromellose, the

results of the in-vitro drug release can be fitted with various kinetic equations like

Zero order

Qt = Q0 + K0t ……………………….(1)

where Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug in the

solution (most times, Q0 = 0) and K0 is the zero order release constant.

First order

log(Qt) = log(Q0) + K1t /2.303………(2)

where Qt is the amount of drug dissolved in time t, Q0 is the initial amount of drug in the

solution and K1 is the first order release rate constant.

Higuchi model

Qt = KH√t ………………………….(3)

KH is the Higuchi‟s release constant


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Hixson-Crowell

Q01/3

- Qt1/3

= KHCt ………………….(4)

where Q0 is the initial amount of drug in the pharmaceutical dosage form, Qt is the remaining

amount of drug in the pharmaceutical dosage form at time „t‟ and KHC is a constant

incorporating the surface–volume relation.

KorsemeyerPeppas

Korsmeyer et al (1983) derived a simple relationship which described drug release from a

polymeric system Eq. (5). To find out the mechanism of drug release, first 60% drug release

data was fitted in Korsmeyer–Peppas model:

Mt/M∞ = KKPtn…………………………(5)

Where Mt / M∞ is fraction of drug released at time t, KKP is the rate constant and n is the

release exponent. The n value is used to characterize different release mechanisms as given in

table 7 [7]

Table 7

Exponent (n) Drug release mechanism

Thin Film Cylinder Sphere

0.5 0.45 0.43 Fickian diffusion

0.5 <n<1.0 0.45<n<0.89 0.43<n<0.85 Anomalous transport

1.0 0.89 0.85 Case-II transport

Patent status

Hypromellose is a choice of polymer used as release controlling polymer in extended release

matrix system. Due to its various properties as mentioned, various pharmaceutical companies

used it in variety of dosage form to prolong the release of drug to extend the life span of the

various drugs. The current patents approved in various countries for

hydroxypropylmethylcellulose in extended release matrix system are about 12000. The

following table illustrates the importance of this polymer. [12]

Table 8: Number of patents approved in different patent offices

Countries Number of patent

ARIPO (African Regional intellectual property organization) 6

European Patent Office 1681

Israel 165

PCT (Patent corporation Treaty) 9205

South Africa 419

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=ARIPO&filterField=CTR&prevFilter=

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=European+Patent+Office&filterField=CTR&prevFilter=

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=Israel&filterField=CTR&prevFilter=

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=PCT&filterField=CTR&prevFilter=

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=South+Africa&filterField=CTR&prevFilter=


565


Table 9: Number of patents approved for companies

Main Applicant Number of patent

THE PROCTER & GAMBLE COMPANY 280

KIMBERLY-CLARK WORLDWIDE, INC. 203

ABBOTT LABORATORIES 156

MONDOBIOTECH LABORATORIES AG 135

ALZA CORPORATION 115

CELGENE CORPORATION 78

HYSEQ, INC. 77

ISIS PHARMACEUTICALS, INC. 76

NOVARTIS AG 76

PROCTER & GAMBLE 74

0

500

1000

1500

2000

2500

Publication Year

Number of Patent

Publication Year 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012

Number of Patent 496 591 705 907 1045 1010 1166 1142 916 994 697

1 2 3 4 5 6 7 8 9 10 11

CONCLUSIONS

Effort to exemplify this polymer over the last four decades has multiplied, yet many

challenges remain unanswered. To date, many diverse techniques have been used to study the

mechanism of drug release from hypromellose matrices. As expertise evolves, there will be

further methods that can characterize hypromellose in a non-invasive manner. Hypromellose

is growing ever more popular as the controlled release polymer of choice.

REFERENCES

1. Dow Commercial Information (2002) Using methocel cellulose ethers for controlled

release of drugs in hydrophilic matrix systems. The Dow Chemical Company, USA, pp

1–36

2. http://en.wikipedia.org/wiki/Semisynthesis

http://patentscope.wipo.int/search/en/result.jsf?query=Hydroxypropyl+methyl+cellulose+and+extended+release+matrix+system&maxRec=11476&filter=THE+PROCTER+%26+GAMBLE+COMPANY&filterField=PAF_M&prevFilter=

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