To Maintain Formulation Composition Similarity of Coated Tablets of Different Strengths: Should Coating be Based on Core Tablet Weight or Surface Area?

PURPOSE: As per the Japanese or SUPAC guidance to maintain formulation composition similarity across tablet strengths, the coating should be applied based on the core tablet surface area or weight, respectively. These two coating approaches were compared by evaluating protective effects of coating on the light stability of three model compounds. METHODS: Core tablets of three light sensitive drugs, nifedipine, rosuvastatin calcium, and montelukast sodium were coated either with PVA-based Opadry® II white or Opadry® II beige. The coated tablets were exposed to light up to three ICH cycles. RESULTS: For Opadry® II white, the surface area based coating provided consistent light protection across tablet strengths when the coating amount was more than 0.1 mg/mm2 compared to that based on core tablet weights. For Opadry® II beige, both approaches gave comparable and better light protection due to presence of iron oxides. The light protection by Opadry® II white could be because of physical barrier of coating, which was uniform across the strengths when it was based on core tablet surface area. CONCLUSION: For a routine tablet formulation development with Opadry color coating, it does not matter whether the coating is applied based on the core tablet surface area or weight.

Quality by design (QbD) approach to match tablet glossiness.

A quality by design (QbD) approach was used for a polyvinyl alcohol (PVA)-based coating to develop a 'look-alike' placebo tablet, which can match the glossiness (shine) of an innovator tablet. Critical coating parameters such as exhaust temperature, drying capacity, solid concentration in coating dispersion, and plasticizer concentration were studied using a full factorial design of experiment (DoE). Total of 20 experimental coating runs was executed on a pilot scale using a perforated pan coater. Coated tablets were evaluated visually against the innovator product by a panel of 13 volunteers using an individual questionnaire about the tablet appearance. The tablet appearance included factors such as tablet surface shine, surface roughness, and logo bridging. These data were analyzed using JMP software. Solid concentration in coating dispersion and drying capacity were found to be the key contributing parameters for tablet surface shine. Human observations were more discerning in spotting subtle differences in tablet appearance than Munsell evaluation. By the judicious selection of a solid concentration in coating dispersion and drying conditions, a look-alike placebo tablet was successfully developed. Change in tablet shape or size did not affect the tablet shine. However, replacement of PVA-based coating with hydroxypropyl methylcellulose (HPMC)-based coating resulted in reduced shine irrespective of tablet shape and size.

Solid-state characterization of lacidipine/PVP K(29/32) solid dispersion primed by solvent co-evaporation.

BACKGROUND: Lacidipine (LCDP) is a 1,4-dihydropyridine derivative categorized as an anti-hypertensive Ca2+ channel blocker having very low solubility, and thus very low oral bioavailability, which presents a challenge to the formulation scientists. Homogeneous distribution of poorly water-soluble drugs like LCDP in polyvinylpyrrolidone (PVP), a hydrophilic carrier, is definitely a suitable way to improve the bioavailability of such drugs. MATERIALS AND METHODS: The aim of the study was to develop a combined thermal, imaging, and spectroscopic approach, and characterize physical state, dissolution behavior, and elucidation of drug-PVP interaction in LCDP/PVP solid dispersion (SD) using differential scanning calorimetry (DSC), X-ray diffractometry (XRD), fourier transform infrared (FTIR) spectroscopy, and hot stage microscopy (HSM), which is the prerequisite for the development of a useful drug product. RESULTS: Dissolution studies of LCDP and its physical mixture with PVP showed less than 50% release even after 60 min, whereas SD of LCDP/PVP ratio of 1:10% w/w showed complete dissolution within 45 min. DSC and powder XRD proved the absence of crystallinity in LCDP/PVP SD at a ratio of 1:10% w/w. The FTIR spectroscopy indicated formation of hydrogen bond between LCDP and PVP. In the SD FTIR spectra, the -NH stretching vibrations and the -C=O stretch in esteric groups of LCDP shift to free -NH and C=O regions, indicating the rupture of intermolecular hydrogen bond in the crystalline structure of LCDP. CONCLUSION: Solid-state characterization by HSM, DSC, XRD, and FTIR studies, in comparison with corresponding physical mixtures, revealed the changes in solid state during the formation of dispersion and justified the formation of high-energy amorphous phase.