1. Introduction
Pharmaceutical microcrystalline cellulose (MCC) is widely used as a filler and binder in oral solid dosage forms. Standard MCC grades such as PH-101 and PH-102 typically have a loss on drying below 5% and can absorb moisture under high-humidity conditions, which may limit their use with moisture-sensitive APIs. For APIs such as vildagliptin and clopidogrel hydrogen sulfate, excess moisture can contribute to degradation, dissolution changes, and stability risks.
PH-112 is a low-moisture grade developed from PH-102 through optimized spray-drying process control. DESU® Microcrystalline cellulose PH-112 uses controlled inlet/outlet air temperatures and atomization conditions to achieve lower initial moisture and improved moisture-control stability. This study evaluates DESU® MCC PH-112 as an MCC excipient for moisture-sensitive API formulations using vildagliptin tablets by direct compression and clopidogrel hydrogen sulfate tablets by dry granulation, with European and American benchmark products for comparison.
2. Experimental Methods
2.1 Physicochemical Indicators and Hygroscopicity Determination
Loss on drying was determined according to Chinese Pharmacopeia standards (dried at 105°C to constant weight). Dynamic vapor sorption (DVS) analyzer was used to measure moisture gain curves in the 0%~100% RH range. At 25°C/35% RH and 25°C/75% RH conditions, moisture absorption weight gain rates were measured using the saturated salt solution method.
2.2 Formulation Process and Evaluation
Vildagliptin Tablets (Direct Compression Process)
Formulation: Vildagliptin 25.0%, PH-112 47.84%, Lactose 23.91%, Sodium starch glycolate 2.0%, Magnesium stearate 1.25%. Powders were mixed (30 Hz, 20 min), then magnesium stearate was added for final blending (30 Hz, 5 min), followed by direct compression (target tablet weight 200 mg). Three pressure gradients were set, and tablet hardness, disintegration time, friability, and dissolution profile (pH 2.0 hydrochloric acid solution) were measured.
Clopidogrel Hydrogen Sulfate Tablets (Dry Granulation Process)
Formulation: Clopidogrel hydrogen sulfate 34.95%, PH-112 20.0%, Mannitol 35.0%, Low-substituted hydroxypropyl cellulose 8.0%, Polyethylene glycol 6000 2.0%, Hydrogenated castor oil 2.0%. Premixed materials were processed by dry granulation (roller speed 2.0 rpm, hydraulic pressure 50 bar), sized, and then compressed (target tablet weight 280 mg, diameter 9 mm). Tablet hardness, disintegration time, friability, and dissolution profile (pH 2.0 hydrochloric acid buffer) were measured.
3. Results and Discussion
3.1 Physicochemical Indicators and Ultra-Low Moisture Characteristics
Table 1 summarizes the physicochemical indicators of three PH-112 products. DESU® MCC PH-112 has a loss on drying of 0.3-0.6%, below the Chinese Pharmacopeia limit of 7.0% and lower than the measured values of the European and American benchmark products (both 0.6%). Its degree of polymerization is 278, compared with 264 and 265 for the two benchmarks, while the pH range of 6.1-6.5 meets the stated 5.0-7.5 requirement.
Table 1 Comparison of Physicochemical Indicators of PH-112 from Different Sources
| Source | Loss on Drying (%) | Degree of Polymerization | pH Value | Bulk Density (g/ml) |
| DESU | 0.3-0.6 | 278 | 6.1-6.5 | 0.29-0.32 |
| European Brand | 0.6 | 264 | 5.8 | 0.33 |
| American Brand | 0.6 | 265 | 6.4 | 0.32 |
Note: Loss on drying standard limit shall not exceed 7.0%
Across four batches, DESU® MCC PH-112 showed loss on drying below 0.6%, with batch-to-batch RSD below 25%, indicating consistent moisture control under the spray-drying process used in this study.
Figure 1 Comparison of Loss on Drying of PH-112 from Different Sources
3.2 Hygroscopicity and Stability Evaluation
DVS testing showed non-linear moisture uptake for DESU® MCC PH-112 across 0-100% RH, with slower growth below 60% RH and faster uptake above 60% RH. At 25°C/35% RH, the material approached equilibrium within 8 hours with approximately 4% weight gain. At 25°C/75% RH, 8-hour moisture gain exceeded 7%.
Figure 2 Moisture Sorption Curves of DESU® PH-112 at Different Humidity
Compared with higher-moisture MCC, PH-112 showed approximately 30-40% lower moisture-absorption weight gain under the same humidity conditions, which the study attributes to its pore structure and surface properties. These results support PH-112 as a low-hygroscopic microcrystalline cellulose option for moisture-sensitive API formulations. The study recommends processing below 35% RH or limiting exposure time to less than 8 hours.
3.3 Vildagliptin Tablet Application Evaluation
Vildagliptin is moisture-sensitive and can degrade after moisture uptake. In the direct compression study, tablets prepared with the three PH-112 products met the stated requirements for weight variation and friability (<0.2%). Under the same main compression pressure, tablet hardness showed no significant difference among DESU, European Brand, and American Brand, indicating that the ultra-low-moisture grade retained compactibility. This supports the use of MCC for direct compression tablets containing moisture-sensitive APIs.
Figure 3 Relationship between Vildagliptin Tablet Hardness and Main Compression Pressure
DESU® MCC PH-112 showed disintegration performance superior to the American benchmark and comparable to the European benchmark. For all three PH-112 products, cumulative dissolution exceeded 85% at 30 minutes in pH 2.0 hydrochloric acid solution, with f2 >50, indicating similar dissolution behavior. The ultra-low-moisture characteristic therefore did not negatively affect the measured formulation performance.
3.4 Clopidogrel Hydrogen Sulfate Tablet Application Evaluation
Clopidogrel hydrogen sulfate is moisture-sensitive and has a tendency to stick to punches. The referenced formulation specifies "low-moisture microcrystalline cellulose." In the dry granulation evaluation, granules prepared with the three PH-112 products showed similar angle of repose (38-42°) and Carr's index (22-26%), with flowability meeting the stated production requirements. This application illustrates the use of MCC for dry granulation and roller compaction in moisture-sensitive formulations.
Across different main compression pressures, tablets prepared with DESU, European Brand, and American Brand PH-112 met the stated requirements for hardness, disintegration time, and friability, with no significant differences. At tablet hardness above 100 N, DESU® MCC PH-112 showed friability below 0.15%.
Table 2 Summary of Application Evaluation of PH-112 from Different Sources in Moisture-Sensitive Drugs
| Model Drug | Process Type | Compressibility | Disintegration Performance | Key Quality Indicators |
| Vildagliptin | Direct Compression | No significant difference among three | DESU® ≈ European Brand > American Brand | Friability <0.2%, Dissolution >85% |
| Clopidogrel Hydrogen Sulfate | Dry Granulation | No significant difference among three | No significant difference among three | Friability <0.15% |
4. Conclusion
DESU® MCC PH-112 has a loss on drying of 0.3-0.6%, below the stated pharmacopeial limit of 7.0%, and is designed as a low-moisture MCC excipient for moisture-sensitive drug formulations. Application evaluations in vildagliptin tablets and clopidogrel hydrogen sulfate tablets showed:
(1) Ultra-low moisture advantage: MCC PH-112 loss on drying is reduced by more than 80% compared to conventional MCC, with controllable moisture absorption weight gain at 25°C/75% RH conditions, suitable for moisture-sensitive APIs.
(2) Preserved formulation performance: Ultra-low moisture did not affect compressibility and compactibility, with performance comparable to competitors in both direct compression and dry granulation processes.
(3) Quality consistency: Multi-batch loss on drying RSD <25%, with good batch-to-batch stability, meeting commercial production requirements.
In summary, DESU® MCC PH-112 is a low-moisture pharmaceutical microcrystalline cellulose grade for moisture-sensitive API formulations. In the vildagliptin direct-compression and clopidogrel dry-granulation models used in this study, it supported moisture control while maintaining the measured tablet-performance attributes.