Hydrochlorothiazide/Losartan Potassium Tablet Prepared by Direct Compression

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Pharmacokinetics

Background:

• Developing fixed-dose combination tablets requires careful optimization of formulation and preparation parameters.
• Understanding powder compression and mechanical properties is crucial for successful direct powder compression tablet manufacturing.

Purpose of the Study:

• To optimize the formulation and preparation of hydrochlorothiazide/losartan potassium (HCTZ/LOS-K) compound tablets using direct powder compression.
• To evaluate the bioavailability of the optimized HCTZ/LOS-K tablets compared to a reference product.

Main Methods:

• Investigation of powder compression and mechanical properties (compressive work, stress relaxation, Py value).
• Application of Kawakita, Shapiro, and Heckel analyses to understand powder compression mechanisms.
• D-optimal mixture experimental design for formulation optimization based on dissolution rate.
• Bioavailability study in beagle dogs comparing optimized tablets with Hyzaar®.

Main Results:

• Lactose monohydrate, microcrystalline cellulose (MCC PH102), and pre-gelatinized starch were identified as key excipients with determined optimal ranges.
• The mixed powder was classified as Class-II, with recommended compaction pressure and tableting speed.
• An optimal formulation (No. 1) was selected based on dissolution rate.
• No significant bioavailability differences were observed between the optimized tablets and Hyzaar® for HCTZ, E-3174, and LOS-K.

Conclusions:

• Direct powder compression is a feasible method for preparing HCTZ/LOS-K compound tablets.
• Combining powder mechanical properties analysis with experimental design effectively determines optimal formulation and preparation factors.
• The optimized HCTZ/LOS-K tablets exhibit comparable bioavailability to the reference product, ensuring therapeutic equivalence.