Amlodipine Besylate–Excipients Interaction in Solid Dosage Form

Abstract

This article studies the compatibility of amlodipine besylate in its solid formulations with various drug excipients. The various factors affecting amlodipine besylate stability were studied using high-performance liquid chromatography (HPLC). It has been found that binary 1:1 mixtures of amlodipine besylate and an excipient are stable at 65 degrees C and 40 degrees C/75% RH. Further investigations were conducted to study the stability of amlodipine besylate in multicomponent mixtures, including mixtures with actual formulations. The study reveals that mixtures of lactose, magnesium stearate, and water induce some instability on amlodipine besylate. The major degradation product confirmed by HPLC-mass spectrometry is amlodipine besylate glycosyl. This is in conformity with the well-known Maillard reaction between primary amines and lactose. Thus, lactose-free amlodipine formulations are recommended from the safety, quality, efficacy, and process cost points of view.

Assessment of Feasibility of Maillard Reaction between Baclofen and Lactose by Liquid Chromatography and Tandem Mass Spectrometry, Application to Pre Formulation Studies

“…This kind of assumption has been previously made by Abdoh et al in the assessment of amlodipine besylate and excipients interaction in solid dosage form (7).…”

“…In formulations, solid-state reactions of the drug substance are of great interest, especially in cases where the drug substance is intrinsically and chemically reactive or unstable (23). Recently, the possible reaction of amine groups of drug entities with carbonyl groups of common tablet excipients, such as lactose, starch, and cellulose has gained a pharmaceutical interest (7,18,(22)(23)(24)(25)(26). Baclofen is an aminecontaining skeletal muscle relaxant, which is used to relieve the signs and symptoms of spasticity due to spinal cord injury or multiple sclerosis (27).…”

“…The later stages are complex and variable, depending on the reaction conditions, and involve further dehydration and fission of the initial reaction products (7). Melanoidines are the final products of the reaction and are actually brown nitrogen containing polymeric substances that decompose with difficulty (8,9).…”

Stability of amlodipine besylate and atenolol in multi-component tablets of mono-layer and bi-layer types

“…Forced degradation studies show amlodipine to be degrading slowly under thermal stress (more in solution than in solid state), degrading faster under photo-stress (more rapidly under UV 366 nm than under 254 nm and less in natural light) and even more under acidic, alkaline and oxidative stress -the highest being in alkaline conditions (6,7). Another pharmaceutical problem is the reported incompatibility in the solid formulation between amlodipine besylate and lactose in the presence of basic excipients (magnesium stearate) and water (8). Atenolol is reported to be photoreactive when exposed to UVA-UVB radiation with photodegradation increasing with a decrease in the pH value.…”

Role of Excipients on N-Oxide Raloxifene Generation from Raloxifene-Excipients Binary Mixtures

“…Many reports are available in the literature that has deliberated the importance of this issue and various methods of compatability testing have been discussed. [1][2][3][4][5] Raloxifene HCl (RHCl), is a selective estrogen receptor modulator shown to be effective in the prevention of osteoporosis, 6) which could be a potential substitute for long-term female hormone replacement therapy. Raloxifene is available as 60 mg tablet under the brand of Evista (Eli-Lilly) and contains 12.5% w/w RHCl, 5% povidone, 6% crospovidone and a combination of other excipients including anhydrous lactose, lactose monohydrate, Tween 80 and magnesium stearate.…”