Sir,
We have reported on the preparation and in-vitro characterization of salbutamol sulfate (SS), tramadol hydrochloride (TH) and diclofenac sodium (DS) microparticles with ethylcellulose (EC) in our previous research articles.[1–3] This presentation summarizes the comparison of dissolution behavior of encapsulated SS, DS and TH (an intradrug and interdrug comparison of their formulation characteristics).
Being a water insoluble polymer, the release of water soluble drug is mainly driven by permeation through the hydrophobic membrane of EC within water-filled pores.[1–3] Thus, the release of TH, SS and DS from their respective microcapsules was influenced by the core to wall ratio. Comparison between dissolution profiles of TH microcapsules showed that 60% of the drug release from its respective microcapsules was achieved in almost 0.86, 1.13 and 1.52 hours, when drug polymer ratio was 1:1, 1:2 and 1:3, respectively. For the same drug polymer ratio, 60% of SS release was achieved after 0.85, 1.44 and 2.93 hours, respectively. Similarly, 60% of the DS release was achieved after 1.70, 2.06 and 2.33 hours, when drug polymer ratio was 1:1, 1:2 and 1:3, respectively. Based on Duncan test, the t60% of all batches of the microcapsules of all drugs lied in the same homogenous group (1:1 = 1:2 = 1:3) (P > 0.05), whereas Tukey Honestly Significant Difference (HSD) similarized the t60% of 1:1 and 1:2 and differentiated them from that of 1:3 but not significantly. On the other hand, Duncan test places these drugs in the following setting based on their t60% of microcapsules: TH = SS = DS (P > 0.05). Tukey test differentiates DS from TH and SS insignificantly on the basis of their t60% of microcapsules. This little difference could be attributed to the nature and solubility differences of these drugs. According to difference factor (f1) and similarity factor (f2), release profiles of the following pairs of microcapsule batches are similar to each other: MTH1 vs. MSS1, MTH2 vs. MSS2, MTH3 vs. MSS3 as their f1 < 15.00 and f2 > 50.00, whereas other compared batches of microcapsules have f1 > 15.00 and f2 < 50.00 that indicates the mutual dissimilarity of the compared release profiles. With a decreasing drug to polymer ratio, the rate of the drug release decreases. It can be assumed that with decreasing drug to polymer ratio, the wall thickness of microcapsules increases which then retards the diffusion of dissolution medium into the microcapsules. The number of surface pores may decrease with increasing polymer concentration (P < 0.05)[1–3].
The observed in-vitro drug release profiles from TH and SS microparticles were biphasic: an initial burst effect and then the slow and prolonged release. The burst effect within therapeutic range may be beneficial because a high initial release produces an instant therapeutic effect which can be subsequently maintained for a prolonged period by a slower but continuous release of these drugs. The rank order of drug:polymer ratios for percentage drug burst was as follows: 1:1 > 1:2 > 1:3, whereas more burst effect is seen in the release profiles of TH than that of SS. The rapid initial phase of release was thought to occur mainly by dissolution and diffusion of drug entrapped close to or at the surface of microparticles. The second and slower release phase may be attributed to the diffusion of drug entrapped within the inner part of the polymer matrix by means of aqueous channels of a network of pores. It has been also been reported[1–3] that an initial burst effect in release profile is observed especially (a) when the drug solubility is high, (b) loading dose in the polymeric matrix is large and (c) when there is lack of critical polymer concentration. Additionally when polymer concentration is low, the hydrated polymeric matrix would be highly porous leading to rapid diffusion of the drug from the polymeric matrix.[1–3]
The release profiles from all the microcapsules were best explained by Higuchi model based on highest linearity, followed by zero order and first order. It suggests that the drug release is controlled by the diffusion of drug through the pores and not through the swollen polymer. From Korsmeyer-Peppas model it is found that the mode of release from all microcapsules was anomalous (non-Fickian, a combination of the diffusion and erosion mechanism) diffusion.
This comparison elaborated that variation observed in entrapment efficiency, production yield, mean particle size and the drug release behavior among the formulations are the result of the nature of drugs and the drug polymer ratio employed. However, this microencapsulation technique was found to be the best for SS and TH compared to DS, in terms of entrapment efficiency, production yield and particle size
References
- 1.Murtaza G, Ahmad M, Asghar MW, Aamir MN. Salbutamol sulphate-ethylcellulose microparticles: formulation and in-vitro evaluation with emphasis on mathematical approaches. DARU. 2009;17:209–216. [Google Scholar]
- 2.Murtaza G, Ahmad M. Microencapsulation of tramadol hydrochloride and physicochemical evaluation of formulations. Pak J Chem Soc. 2009;31:511–519. [Google Scholar]
- 3.Murtaza G, Ahmad M, Shahnaz G. Microencapsulation of diclofenac sodium by non-solvent addition technique: Use of toluene and petroleum benzin as solvent and non-solvent respectively. Trop J Pharm Res. 2010;9:187–195. [Google Scholar]
