May 22, 2026

Easy Sustained Release Drug Delivery Formulations Using High Viscosity HPMC (Hypromellose) in Oral Dosage Forms

Why developing sustained release formulations?

Sustained release (SR) pharmaceutical formulations are designed to release a drug at a controlled and consistent rate over an extended period. Unlike conventional drug formulations, which release the active ingredient rapidly and often require frequent dosing, sustained-release products are engineered to maintain therapeutic plasma concentrations with fewer doses. This results in improved patient compliance, enhanced therapeutic efficacy, and a reduction in side effects caused by drug peaks and troughs in the bloodstream.

Sustained-release formulations are particularly beneficial for drugs that require long-term management of chronic conditions or those that have a short half-life. By providing a steady release of medication, SR formulations ensure that patients receive optimal drug levels throughout the day, minimizing fluctuations that could lead to suboptimal therapeutic effects or adverse events.

The technology behind sustained-release systems varies, but the most common methods involve creating formulations where the drug is embedded in a matrix or coated with materials that control its release. These formulations are often achieved using polymers, such as Hydroxypropyl methylcellulose (HPMC), which are able to form gels or other structures that slow the drug’s release over time [1].

Principles of Sustained Release with HPMC

HPMC is a hydrophilic, non-ionic cellulose ether that forms a gel layer upon contact with water, controlling drug release via:

Hydration & Gel Formation – When the tablet encounters aqueous fluids, HPMC hydrates and swells, forming a viscous gel layer around the tablet core.
Diffusion-Controlled Release – The drug diffuses through the gel layer at a rate dependent on its solubility as well as viscosity and polymer concentration.
Erosion-Controlled Release – The outer gel layer gradually erodes, releasing the drug in a controlled manner.

Figure 1. Principles of Sustained Release with HPMC depicted as a step wise process.

Selection of Hypromellose grades and conditions for hydrophilic matrix system

Critical control parameters for hydrophilic matrix formulations with Hypromellose:

Drug solubility
The solubility of the drug determines its primary release mechanism from a hydrophilic matrix. For highly soluble drugs, release is mainly governed by diffusion through the hydrated Hypromellose gel layer. In contrast, poorly soluble drugs rely more on the erosion of the gel matrix for their release, as their limited solubility hinders effective diffusion.
Hypromellose viscosity
The viscosity grade of Hypromellose (HPMC) affects the gel layer formed upon hydration. Higher viscosity grades create thicker, more viscous gels, which slow down water penetration and drug diffusion, resulting in a slower release. Lower viscosity grades promote faster dissolution.
Hypromellose content
The amount of Hypromellose in a formulation plays a crucial role in controlling drug release. Higher HPMC content leads to the formation of a thicker gel layer upon hydration, which slows drug diffusion and prolongs release. Conversely, lower content results in a thinner barrier, allowing faster release. Importantly, a homogeneous distribution of Hypromellose within the tablet matrix is essential to ensure uniform gel layer formation. This uniformity helps achieve consistent drug release and prevents localized variations that could lead to dose dumping or incomplete release or even initial burst effect.
Hypromellose substitution types
Variations in Hypromellose’s chemical substitution (e.g., methoxy and hydroxypropyl groups) influence its hydration behaviour, gel strength, and overall matrix structure. These differences affect the rate at which water penetrates the matrix and, consequently, the drug release profile. The hydration time is particularly important, as faster-hydrating substitution types (HPMC type 2208) form gel layers more quickly, providing immediate control over drug release. In contrast, slower-hydrating types (HPMC type 2910) may delay gel formation, potentially leading to an initial faster dissolution profile, burst release or inconsistent dissolution.

How to use Hypromellose for hydrophilic matrix system

Hydrophilic matrix tablets can be prepared using either direct compression (DC) or wet granulation (WG).

Direct compression
METOLOSE® and TYLOPUR® 90SH-SR have sufficient flowability and compressibility to serve as an optimal hydrophilic matrix component in the direct compression. If the remaining compounds of the formulation do not significantly decrease these properties the formulation can be subjected to direct compression.
Wet granulation
If the flowability of the API is a bottleneck (especially in a high load formulations) matrix tablets can be made using wet granulation step. Granulation can be performed using solvent/water mix (for example 80:20 % of ethanol) in a standard equipment, for example in a high shear mixer.

Pros and Cons of High Viscosity HPMC in SR Formulations

Advantages

✅ Widely accepted – FDA-approved, GRAS (Generally Recognized as Safe) status.

✅ Flexible release profiles – adjustable by varying viscosity grade and concentration of HPMC.

✅ Simple formulation – requires only API, HPMC lubricant and filler (if necessary)

✅ Direct Compression (DC) – good flowability and compactibility of HPMC allows for the direct compression.

✅ Wet granulation (WG) – wet granulation with solvents possible for more demanding formulations.

✅ High API load – able to accommodate high levels of drug loading

✅ Compatibility – works with a broad range of APIs due to its non-ionic nature (e.g., metformin, pseudoephedrine, theophylline).

✅ Cost-effective – cheaper than some synthetic polymers.

✅ Non-toxic – safe for oral use.

Disadvantages

❌ Sensitivity to some excipients – some fillers may influence the final dissolution rates of the API in the HPMC hydrophilic matrix systems.

Conclusion

Hypromellose (HPMC) remains a widely trusted and versatile polymer for sustained-release (SR) oral formulations, thanks to its consistent gel-forming ability, safety profile, and adaptability across various drug types. High-viscosity grades, such as those used in metformin SR tablets, provide effective modulation of drug release through matrix hydration and gel barrier formation, thereby enhancing therapeutic efficacy while mitigating gastrointestinal side effects. The successful design of SR formulations hinges on the rational selection of HPMC viscosity grade and precise optimization of polymer concentration to achieve desired release kinetics and ensure batch-to-batch consistency.

References:

[1] Hydrophilic matrix tablets for oral controlled release; Timmins, P., Pygall, S.R., Melia, C.D. (Eds.). 2014, IX, 323 p. 102 illus., 37 illus in color., Hardcover, ISBN: 978-1-4939-1518-7.

[2] Bose S, Kaur A, Sharma SK. A review on advances of sustained release drug delivery system. Int Res J Pharm 2013; 4(6): 1-5.

[3] Handbook of Pharmaceutical Excipients (Rowe et al.)