Hydroxy propyl methyl cellulose (HPMC) 5cPs, an aqueous soluble polymer was employed for coating diclofenac sodium (DFS) tablets 25 mg for protecting the integrity of the drug yet rendering the drug to release at a faster rate on contact with the gastric environment. Proper optimization for the aqueous based film coating formulation was undertaken primarily employing plasticizers like polyethylene glycol (PEG) 400 and propylene glycol (PG). The defect free selected formulations were further subjected for studying the effects of surfactants like sodium lauryl sulphate (SLS) and Tween-80 along with the plasticizers. The quality of the aqueous film coats or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3% which can be stated on the basis of less incidence of major coat defects like chipping, cracking, orange peel, roughness, blistering, blooming, picking. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. Elegant film formation can be stated from fewer incidences of coat defects. The obtained coated tablets eventually satisfied all the normal physical parameters like thickness, weights, and weight gain, drug content, crushing strength, percent friability, disintegration time, dissolution profile and possible drug–polymer interactions. ANOVA was undertaken followed by Dunnet multiple comparison for the dissolution profile considering uncoated as the standard. The difference was considered significant at p ⩽ 0.01.
Keywords:
Aqueous film coating, Diclofenac sodium tablets, Plasticizer, Surfactants
Film coating is a complex process that involves different factors. To ensure spreading and/or film forming capability plasticizers are added. The type and concentration of plasticizers can affect the film properties, as revealed by several investigations (Mortada, 1990; Siepmann et al., 2005; James, 1997). The plasticizing efficiency is measured by the lowering of the incidence of coat defects. In this study two plasticizers namely polyethylene glycol 400 (PEG-400) and propylene glycol (PG) were selected. Aqueous film coating liquid was prepared by incorporating different concentrations of PEG-400 and PG (Mortada, 1990; Muschert et al., 2009; Abdul-Razzak and Aulton, 1984).
As the viscosity of the coating solution increases, there is greater resistance to spreading on the substrate surface and reduced tendency of the droplets to coalesce, both of which increase surface roughness. Other factors arising from an increase in solution viscosity, which may potentiate surface roughness, include the larger mean droplet size on atomization and the reduced penetration into the uncoated tablet or multiparticulate surface (Siepmann et al., 2007; Felton, 2007; Herbert et al., 1990). Variation in solution viscosity may also affect the rate and extent that a coating formulation penetrates into a substrate during the application. Difference in penetration behavior may be important in determining the adhesion of the coat to the substrate (James, 1997; Hossain and Ayers, 1990; Lippold et al., 1990). Little or no penetration may lead to poor adhesion. Invariably a tablet formulation includes lubricants to improve flow properties of the granules and to overcome certain processing problems. These ingredients are hydrophobic and in fine state of subdivision, present on the surface of the tablet which may hinder penetration of the coating liquid/solution. It is therefore prudent to include surfactants of high HLB value at smaller concentration, to improve penetration and spreading properties of the coating liquid.
The objective was also to investigate the effects of surfactants on the coating uniformity and quality of the film coat. In this study two surfactants of high HLB value such as sodium lauryl sulphate (SLS) and Tween-80 were selected and incorporated at different concentrations in the coating solutions (Mortada, 1990).
Diclofenac sodium (DFS), a phenyl acetic derivative, is an NSAID, mainly used to treat different pain managements and inflammation in various conditions; musculoskeletal and joint disorders such as rheumatoid arthritis, osteoarthritis and ankylosing spondilytis. DFS is also effective against peri-articular disorders, soft tissue disorders and other painful conditions such as renal colic, acute gout, dysmenorrhoea, migraine, and surgical procedures. The usual dose of the drug is 75 to 150 mg orally or rectally. The terminal half-life of DFS is about 1 to 2 h. DFS at a low dose of 25 mg can also be formulated in the form of immediate release tablets as an over the counter (OTC)/non-prescription drug to counteract different pain managements. This is due to the fact that DFS is the only salt that has enough safety and pharmacovigilance data that supports RX to OTC switch strategy (Moore, 2007; Rigato et al., 2009; Motola et al., 2001). Coating of DFS is necessary to prevent photolytic degradation and masking of its unpleasant taste.
Our present study is aimed in the preparation of a 25 mg DFS tablet and subsequent development of an optimized film coating formula after properly studying the effects of plasticizer and surfactants for the purpose of coating the tablets (Motola et al., 2001; Morkhade et al., 2008).
The tablets were prepared in an environment free from organic solvents. From the results it can be stated that plasticizers like PEG-400 at 1.5% and PG at 1% have a significant effect on the film forming property of HPMC. The films formed with HPMC + PEG400 (1.5%) were free from major defects like cracking, orange peel, and picking with good gloss and very slight chipping and splitting occasionally (Mortada, 1990; James, 1997; Hossain and Ayers, 1990). In regard to HPMC + PG (1%) the resultant films were free from defects such as roughness, picking, orange peel and cracking, having good gloss and slight chipping. Uniformity in tablet weight gain and thickness of the film coat data obtained from cast film measurements are supportive for elegant film formation. The quality of aqueous film coat or the plasticizer efficiency in case of PEG-400 is in the order 1.5 > 0.5 > 1.0% and for PG 1 > 4 > 3%. This preliminary study infers that plasticizer significantly influences the quality of aqueous film coats. The best formulations (F3 and F4) are selected for further trials. Two surfactants of high HLB value namely SLS and Tween-80 were tried for bringing uniformity in the spreading efficiency on the substrate surface. It was found out that among the six formulations containing SLS, F3B (HPMC + PEG 1.5% + SLS 0.3%) yielded the most satisfactory result. The films were found to be free from blistering, blooming, chipping, cracking, picking, orange peel, roughness, splitting with uniform color distribution and good glossy appearance. On the other hand with the six formulations of Tween-80, F4E (HPMC + PG1.0% + Tween-80 0.3%) yielded the most satisfactory result. The films were found to be free from blistering, chipping, cracking, picking, orange peel, roughness, splitting with slight blooming, uniform color distribution and good glossy appearance. The quality of aqueous film coat or the surfactant efficiency in case of SLS + PEG-400 is in the order 0.3 < 0.5 < 0.1% and SLS + PG is in the order 0.5 < 0.1 < 0.3%. In case of Tween-80 + PEG-400 the order is 0.3 < 0.5 < 0.1% and Tween-80 + PG is in the order 0.3 < 0.1 < 0.5%. From this study it may be concluded that surfactants of high hydrophilic nature might be useful in improving the film coating liquid properties to achieve better spreading and resulting in better quality film coats.
The normal characterization of the granules like angle of repose, moisture content, and bulk density was found to be normal within the acceptable limits stated in . Evaluatory parameters of the coated tablets like thickness, weight, diametral hardness, and friability were found to be within the normal limits as stated in .
The total disintegration time of all the selected tablets was found to be within 2 min 30 s (F4B) to 3 min 30 s compared to the uncoated 2 min 20 s in 0.1(N) HCl. This suggests that there is no abnormality for the drug to disintegrate in its specified environment.
The in vitro release data of all formulations were fitted in zero order and the rate constants and correlation coefficient were compared to get a trend in the release pattern of the drug from the formulations. From it is evident that the selected batches F4B and F4E predominantly shows a zero order profile releasing the DFS within 1 h 30 min which eventually satisfies the percentage release. The initial bursting effect of the film coats was obtained in between a time span of 5 min and leaching of the API was observed. The cumulative percent release within 5 min after examination was found out to be in the order F4B > F4E > F4 > F3 > F4C which suggests the proper functioning of the films.
From the infrared spectra it is clearly evident that there were no interactions of the drug with the polymer. The main peaks in the spectrum of the drug DFS, both uncoated and coated does not show any substantial difference. The IR spectra show a peak at 746.18, which signifies the presence of N–H (rocking) functional group. A peak is also observed at 1651.12 wave number, which signifies the presence of C–C (stretch). Simultaneously a peak at 746.48 signifies the presence of C–Cl (stretch). All these peaks were observed at the fingerprint region of the FT-IR spectra. This proves the fact that there is no potential incompatibility of the drug with the polymer (HPMC 5cPs) used in the formulations. Hence, the formula for preparing DFS (25 mg) coated with HPMC 5cPs tablets can be reproduced in an industrial scale without any apprehension of possible drug–polymer interactions.
SEM study further confirmed the proper erosion and diffusion mechanisms to be operative during drug release from the optimized batch of HPMC 5cPs coated DFS tablet (F3B). SEM photomicro-graphs of the tablets at different time intervals after the dissolution experiment showed that tablets were intact and pores had formed through the surface ( ). Photomicrographs from SEM at definite time intervals 0, 30 min, (A, B) revealed pores with increasing diameter. The photomicro-graphs also revealed formation of gelling structure (C) indicating the possibility of swelling and eroding of the tablets.
In conclusion, tablet coating films made of HPMC 5cPs with the addition of PEG at 1.5% and SLS at 0.3% and films made of HPMC 5cPs with PG at 1% and Tween-80 at 0.3% could be considered as an elegant film forming formulation for solving different coating problems generally faced in an industrial scale. The film coating formulations were entirely prepared in an aqueous environment avoiding the environmental unfriendly toxic hazards accompanied with organic solvents. These optimized formulations could be further developed in an industrial scale for the purpose of coating immediate release formulations for those drugs whose integrity needs to be protected from sunlight, oxidations, moisture, thermolability and foreign microbial attack. The concept of Rx to OTC switch strategy (Moore, 2007; Rigato et al., 2009), for the proven safest salt of diclofenac can be eventually satisfied by the use of such selected formulations for the purpose of coating.
Open in a separate windowAuthors wish to thank Roland Pharmaceuticals (Berhampore, India) for providing gift sample of diclofenac sodium. We are also thankful to the staffs of Himalayan Pharmacy Institute (Sikkim, India) for their helps they have extended during the FT-IR study. We are also thankful to B.I.T., Meshra, Ranchi, for their relentless cooperation of SEM works.
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