A Novel Application of an Effervescent Agent in Naproxen Liqui-Pellets for Enhanced Drug Release

Pubdate：2023-06-25　Click：229

Matthew Lam* and Ali Nokhodchi

Pharmaceutics Research Laboratory, School of Life Sciences, University of Sussex, Brighton, UK.

ABSTRACT :Liqui-Pellet formulations have been introduced as a technology to improve the dissolution rate of poorly water-soluble drugs. This study aimed to incorporate sodium bicarbonate (NaHCO₃) into the Liqui-Pellet formulation to explore the potential impact on the drug release rate. Naproxen Liqui-Pellet formulations containing 5%, 12%, 22%, 32%, and 42% w/w of NaHCO₃ were successfully produced and their physicochemical properties were investigated and compared with a physical mixture pellet formulation. Incorporation of such a large amount of functional excipient is impossible or near impossible in the classical liquisolid formulation due to weight and size limitations, particularly for high-dose drugs. The results showed that NaHCO₃ is an effective functional excipient to enhance the drug dissolution rate. The Liqui-Pellet formulation with 42% w/w NaHCO₃ released 76.4% of drug after 2 hours atpH 1.2, which was 14 times faster than the physical mixture pellet (5.5% drug release in 2 h). In general, a faster dissolution rate was observed with increasing NaHCO₃ concentration; however, there was a limit to this effect. Above a certain limit, the influence of NaHCO₃ on the dissolution rate lessened. The flowability test showed that all formulations have good to excellent flowability. Overall, this study demonstrates the flexibility of Liqui-Pellets in terms of formulation design, which in turn further supports the potential of Liqui-Pellets as the next generation oral dosage form.

KEYWORDS: Liqui-Pellet, Liqui-Mass system, liquisolid, effervescent agent, dissolution enhancement

CONCLUSION: This study proved that it is feasible to embed an effervescent agent into LP formulation, whilst obtaining excellent or good flow property and yet keeping the overall dosage form small and light enough for swallowing. The incorporation of 42% NaHCO₃ in the formulation made the total weight of each capsule unit containing LPs to be only 231 mg. This would have been very difficult or near impossible to achieve with liquisolid technology, particularly in a high-dose drug, where a high liquid load factor would result in a heavy and bulky formulation due to increase carrier and coating material being required, let alone the addition of functional excipients. The dissolution test results show a considerable increase in the drug release rate with NaHCO₃, where such formulations are around 14 times faster than a physical mixture pellet after 2 hours. As NaHCO₃ concentration increases, so does the drug release rate; however, there is a limit to how much NaHCO₃ can be added before its influence on the drug release rate lessens. Therefore, it is imperative to know this limit to balance the weight of capsule and drug release performance into an ideal dosage form. The data from this investigation verifies that the effervescent LP can achieve good robustness and excellent or good flow properties with narrow particle size distribution. Overall, the results support the potential for taking the concept of a liquid API in a solid matrix dosage form in a commercial direction. Future study will include investigating the feasibility of effervescent LPs in high-dose formulation. 

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