The research study provides an insight into different manufacturers' microcrystalline celluloses (MCC) thorough characterization, comprising determination of morphology, PSD, percentage crystallinity, surface area, true density, crushing strength, and compaction behavior. The study indicated good compaction, crushing strength for Ceolus KG 1000 and Emocel 50 M. Different varieties of MCC exhibited consistent mean yield pressure and crushing strength irrespective of their percentage crystallinity, degree of polymerization, and moisture content. The impact of these MCC characteristics was evaluated in formulations containing high and low-dose lactose incompatible drugs. Ceolus KG 1000 showed better compressibility, crushing strength and devoid of capping when used in acyclovir (high-dose) formulation. However, drug release of amlodipine (low-dose) formulation was significantly reduced when >80 % w/w Ceolus KG 1000 used. Amlodipine formulation with Emocel 50 M showed faster drug release. On statistical evaluation, surface area and true density were found to be significant factors for mean yield pressure and crushing strength of acyclovir formulations. PSD, true density, and bulk density were found to be significant factors affecting release of amlodipine formulations. Study showed that characteristics of Ceolus KG 1000 and Emocel 50 M are favorable for acyclovir and amlodipine formulation, respectively. Lastly, study suggests that vendor change of MCC might be unfavorable if not evaluated properly for both formulations containing high and low-dose actives.