Healthcare
METOLOSE® SR have an optimized viscosity, hydroxypropoxy content, and particle size to guarantee highly reproducible dissolution profiles in the production of extended release matrix tablets. They are compliant with USP, JP, EP and easy applicable in granulation or direct compression (DC) processes. Different viscosity grades of METOLOSE® SR are available according to your requirement.
METOLOSE® SR grades are hypromellose substitution type 2208 (also name as Hydroxy propyl methyl cellulose or HPMC). Hydroxypropoxy and methoxy groups are added on the cellulose backbone leading to a water soluble cellulose derivative suitable for hydrophilic matrix tablets formulations.
| Grades | Description | Regulatory | Origin | Knowledge Base | |
|---|---|---|---|---|---|
| 90SH-100SR | Hypromellose 2208, 100 mPas, sustained release | USP, EP, JP | Japan | Select | |
| 90SH-4000SR | Hypromellose 2208, 4000 mPas, sustained release | USP, EP, JP | Japan | Select | |
| 90SH-15000SR | Hypromellose 2208, 15000 mPas, sustained release | USP, EP, JP | Japan | Select | |
| 90SH-100000SR | Hypromellose 2208, 100000 mPas, sustained release | USP, EP, JP | Japan | Select | |
The hydrophilic matrix system is one of the simplest way to sustain the release of active pharmaceutical ingredients (API) into the body. It is especially useful to maintain the API release within the therapeutical window. As a result, the daily intake of tablets as example can be reduced leading to a better patient adherence to the medicine. METOLOSE® SR high viscosity grades of Hydroxy propyl methyl cellulose 2208 (90SH-SR types) can be used as a hydrophilic matrix agent. Shin-Etsu provides a tighter specification which is especially suitable for sustained release formulations and guaranty consistency and reproducibility in the final product.
The dissolution steps of a matrix tablet is presented in the figure below. Hydroxy propyl methyl cellulose matrix tablets hydrate to form a gel layer, which regulates the API release pattern. The most important aspect of this matrix system is the homogeneity of the HPMC particle size distribution in the tablet as the selection of the substitution types will affect the initial wetting, swelling, hydration and gel strength.
Several factors should be considered for the formulation of matrix tablets, such as:
API Solubility |
|
HPMC Properties |
|
Formulation |
|
Preparation |
|
Solubitity in water: In case of a highly water-soluble drug, drug release is regulated by diffusion through the gel layer. For a poorly water-soluble drug, the drug release is regulated by erosion of the matrix tablet.
pH dependency: The dissolution profile of same matrix tablets is similar in different media, this shows that the dissolution profile is independent of pH.
Effect of substitution type: Substitution type of HPMC affects hydration speed of HPMC particles and gel strength, which can influence the dissolution profile. Comparing different substitution types; HPMC 2910 , HPMC 2906 and HPMC 2208 (METOLOSE® 90SH-SR grades), a slower release is obtained when a HPMC with a lower methoxy content is used.
Viscosity variation: The viscosity of Hydroxypropylmethyl cellulose affects gel strength, hydration speed in the first stage and erosion rate of the gel in the second stage. The higher viscosity grade has stronger gel strength and slower dissolution.
Hydroxypropylmethyl cellulose content: The content of HMPC in the matrix tablet has a significant effect on the dissolution profile. It affects the initial erosion of the tablet (first stage). Shin-Etsu recommends 20 % to 40 % content of METOLOSE® SR for the matrix tablet in order to obtain a delayed release.
Fillers consideration: Hydrophilic matrix tablet formulations require the API, the matrix polymer (HPMC 2208, METOLOSE® SR) and the lubricant. Fillers can be added to the matrix tablets to achieve suitable tablet weight and modify compressibility and powder flow. Three popular fillers are lactose, microcrystalline cellulose, and calcium phosphate. Depending on the nature of the filler, different dissolution profiles are observed. The effect of the filler on the dissolution profile of matrix tablets is different according to the dissolution media used.
Matrix tablets are easily prepared with active ingredient and METOLOSE® SR (Hypromellose 2208) by different methods such as direct compression (DC), wet granulation and dry granulation. DC is the most cost-effective production method and can be applied if the components of the formulation (such as API) have the following properties: sufficient flowability, sufficient compressibility and miscibility with METOLOSE® SR. These materials have sufficient flowability and compressibility to be used by DC. However, in case the other ingredients do not have the desired properties for the direct compression method, intermediate steps of wet or dry granulation are needed. Standard equipments such as High Shear Mixer, Fluid Bed and Roller Compactor, should be used. For wet granulation, a mixture of water and ethanol (20:80 by wt.) is recommended as a solvent.
METOLOSE® SR can also be used for other applications as Plaster/Dermal patches as mentioned in our guide of application - table below.
| Application |
|---|
| Tablets & Pellets |
| Sustained release (matrix tablets) |
| Liquid and Others |
| Plaster/ Dermal Patch |
| Continuous Manufacturing (CM) for Oral Solid Dosage Form (OSD) |
| Wet granulation (WG) sustained release (SR) |
| Roller compaction (RC) sustained release (SR) |
| Direct compression (DC) sustained release (SR) |
| METOLOSE® SR | |||
|---|---|---|---|
| 90SH-100SR | 90SH-4000SR | 90SH-15000SR | 90SH-100000SR |
| •• | •• | •• | •• |
| • | • | • | • |
| •• | •• | •• | •• |
| •• | •• | •• | •• |
| •• | •• | •• | •• |
• Suitable / •• Very Suitable
Shin-Etsu has 20 Technical documents available regarding Hydroxy propyl methyl Cellulose for Sustained Release applications; such as:
More information on the applications of METOLOSE® SR can be found here.
The Shin-Etsu team is supporting in all technical, quality and regulatory related questions. Our team of sales and technical sales manager can help you to develop your products, or provide support during issues at your manufacturing process. Shin-Etsu has long year experience in cellulose ether business and is aiming to give you the best possible guidance and high quality products manufactured in Japan and Germany.
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