Masking the Bitter Taste of Injectable Lidocaine HCl Formulation for Dental Procedures

Abstract

Abstract. Several attempts have been made to mask the bitter taste of oral formulations, but none have been made for injectable formulations. This study aims to mask the bitter taste of dental lidocaine HCl (LID) injection using hydroxypropyl-β-cyclodextrin (HP-β-CD) and sodium saccharin. Inclusion complexes of LID and HP-β-CD were prepared by the solution method in 1:1 and 1:2 M ratios. Inclusion complexes in solution were studied using phase solubility in phosphate buffer solutions (pH 8, 9, and 10). Freeze-dried inclusion complexes were characterized using differential scanning calorimetry (DSC), Xray, Fourier transform infrared (FT-IR), nuclear magnetic resonance (NMR), scanning electron microscopy (SEM), and in vitro release. Injectable formulations were prepared using inclusion complexes and characterized for stability and for taste using an Alpha MOS ASTREE electronic tongue (ETongue). The association constants of HP-β-CD with lidocaine-free base and its ionized form were found to be 26.23± 0.00025 and 0.8694±0.00045 M −1 , respectively. Characterization studies confirmed the formation of stable inclusion complexes of LID and HP-β-CD. Injectable formulations were found to be stable for up to 6 months at 4°C, 25°C, and 40°C. The taste evaluation study indicated that HP-β-CD (1:1 and 1:2 M ratios) significantly improved the bitter taste of LID injectable formulation. In conclusion, inclusion complex in the 1:1 M ratio with 0.09% sodium saccharin was considered to be optimum in masking the bitter taste of LID.

Cyclodextrins as Emerging Therapeutic Tools in the Treatment of Cholesterol-Associated Vascular and Neurodegenerative Diseases

“…These molecules, synthetized by enzymatic cleavage of starch, have extensively been used worldwide in numerous industrial production processes in food, cosmetics, agriculture, environment, medicine and chemistry. In the pharmaceutical area the formulations of an increasing amount of marketed drugs include CDs due to their capacity to enhance drug solubility, drug bioavailability, and chemical stability [6][7][8] in addition to their diminished cell toxicity and the capability to mask the bitterness of many active compounds or adjuvants [9]. This has been related to the physicochemical structure of CDs able to trap drug candidates into their cavity enabling their use in drug delivery to facilitate body tissue penetration of hydrophilic or hydrophobic drugs.…”

Effects of lidocaine and the inclusion complex with 2-hydroxypropyl-β-cyclodextrin on cell viability and proliferation of oral squamous cell carcinoma

“…The complete characterization of the HP-b-CD-lidocaine complex has already been demonstrated in previous studies applying, in addition to DSC and SEM, other techniques such as the phase solubility study, power X-ray diffractometry, nuclear magnetic resonance, Fourier-transform infrared spectroscopy, in vitro release and others methods. [21,22] Drug delivery systems act as reservoirs delaying the release of the local anaesthetic. Thus, the complexation in HP-b-CD can enhance the pharmacological properties of lidocaine, avoiding its dispersion from the injected site.…”

“…The complexation of LA in cyclodextrins provides pharmacological improvements and therapeutic benefits, by slowing the drug release, increasing anaesthetic duration, and reducing its toxicity . The 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CD) is a hydroxy‐alkylated β‐CD derivative with excellent aqueous solubility and satisfactory inclusion capacity, which has demonstrated the ability to form a stable complex with lidocaine …”

“…[19,20] The 2-hydroxypropyl-b-cyclodextrin (HP-b-CD) is a hydroxy-alky lated b-CD derivative with excellent aqueous solubility and satisfactory inclusion capacity, which has demonstrated the ability to form a stable complex with lidocaine. [21,22] The main hypothesis of this study is that lidocaine exerts cytotoxic effects on oral squamous cell carcinoma. This effect is probably improved by its complexation with HPb-CD.…”

Traditional Human Taste Panel and Taste Sensors Methods for Bitter Taste Masking Research on Combined Bitterness Suppressants of Berberine Hydrochloride

“…(1) Some of the most commonly used bitter-tasting drugs include aspirin, naproxen, and quinine. Recently, research into drug taste masking has been highlighted in the popular press (2)(3)(4)(5) with taste masking using bitterness suppressants (BSs) as an important topic. (6)(7)(8)(9)(10) BSs compensate for the bitter substance by blocking bitter taste receptors, truncating the bitterness signal transmission or by offering an even greater signal to the sweet receptors.…”