New insight into single phase formation of capric acid/menthol eutectic mixtures by Fourier-transform infrared spectroscopy and differential scanning calorimetry

Purpose: To examine the structural changes of a eutectic mixture comprising capric acid and menthol which are commonly used in pharmaceutical applications. Methods: A phase diagram was constructed by quantitative mixing of capric acid and menthol under controlled conditions until a single liquid phase was formed. Eutectic mixtures of capric acid: menthol at the ratios of 3:2, 1:4, 1:1, 2:3, and 1:4 were prepared. Hydrogen bond formation and conformational changes were analyzed using Fourier-transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). Microscopic imaging was carried out to capture phase change events upon increasing temperature. Results: Menthol confirmed the intact structure of a hexagonal ring. The high degree of broadening of the menthol O-H groups indicates hydrogen bond formation. FTIR band changes related to capric acid suggest a break-up of the methylene arrangement structure due to changes in the C-H band frequencies. The red shift encountered in C=O stretching band emphasizes hydrogen bond formation taking place between the oxygen atom of the hydroxyl group comprising the carboxylic moiety of capric acid and the hydrogen atom of menthol hydroxyl group. DSC results indicate the presence of two polymorphs of the capric acid/ menthol complex. Both exhibited crystallization and conformational change exotherms in addition to two melting endotherms as result of transformation of crystalline components to become partially crystalline due to hydrogen bond formation. Conclusion: The interaction between capric acid and menthol results in a typical preparation of deep eutectic systems that can act as natural-based solvents in numerous pharmaceutical applications. Keywords: Eutectic system, Capric acid, Menthol, Differential scanning calorimetry, DSC, Fourier transform infrared spectroscopy, FTI

Using chitosan and xanthan gum mixtures as excipients in controlled release formulations of ambroxol HCl - in vitro drug release and swelling behavior

Directly compressed matrices were produced using a binary mixture of different chitosan (CH) and xanthan gum (XG) ratios. These hydrophilic excipients were used to control the release of ambroxol HCl. CH and XG were investigated at three ratios of 1:1, 1:4 and 4:1. Mucosolvan LA® was used as a commercially available reference product. The optimal CH to XG ratio was 1:1 and the optimal drug to polymer ratio was 1:3. Matrix erosion, hydration and drug release studies were carried out using a dissolution apparatus (basket method). The release mechanism is also discussed

Application of an excipient made from chitosan and xanthan gum as a single component for the controlled release of Ambroxol

An oral controlled release (CR) matrix system of Ambroxol hydrochloride was developed using a binary hydrophilic polymer mixture of chitosan (CH) and xanthan gum (XG) (1:1 w/w ratio). Two test tablet formulations were prepared using drug to polymer mixture ratios (D:P) of 1:1 and 1:3 (w/w), designated as T1 and T2, respectively. The in vitro drug release data was best fitted to the Higuchi equation. The 1:1 ratio (T1) demonstrated in vitro dissolution similarity with the commercial product, Mucosolvan LA. A preliminary in vivo study was performed using six volunteers. The study was designed to include open, randomized, singledose, three-treatment, six-sequence, crossover (Williams design) under fasting conditions. The data showed that T1 was bioequivalent to Mucosolvan LA ® after the administration of a single 75mg oral dose. Two in vivo, in vitro correlations (IVIVC) were established between Cmax versus the fraction of drug dissolved (FRD) after 4 hours, and AUC versus the ratio of fraction of drug dissolved (FRD) after 10 hours where a multiple point level C correlation of IVIVC was obtained

DETERMINATION OF HYDROLYSIS PARAMETERS OF YOHIMBINE HCl AT NEUTRAL AND SLIGHTLY ACIDIC MEDIUM

Objectives: In the process of investigating various new drug delivery systems of yohimbine HCl (Yoh), it was necessary to study some of the physical chemical properties of the drug including its stability at neutral, acidic and slightly acidic conditions.Methods: A validated HPLC method was developed and employed for analysis of Yoh containing solutions. The mobile phase composed of 60% menthol: 40% NaOAc (%v/v), and Gemi C18 column, 5 µm particle size was used as a stationary phase. The degradation product was found to be yohimbinic acid (YA). The retention times for Yoh and YA were 5 and 3 minutes, respectively. This study investigated the kinetics of hydrolysis of Yoh at pH 6.0 and 7.0 at temperatures from 50 °C to 80 °C.Results: The reaction followed first order kinetics and the activation energy ∆E of the reaction at pH 6 and pH 7 was found to be 16.2 and 16.8 Kcal. mole-1, respectively. While the values of A were found to be 41.8 and 44.1 Kcal. mole-1 at pH 6 and 7, respectively. The pseudo first order rate constants (K) at pH 6 and 7 were calculated as 2.76 Ñ… 10 -3 h-1 and 3.42 Ñ… 10 -3 h-1, respectively.Conclusion: Such results indicate high stability of the drug at these pH values. At highly acidic medium the reaction was found to be extremely slow indicating the absence of acid catalysis on the hydrolysis of Yoh. Thus, the yohimbine ester group resists hydrolysis in highly acidic conditions.Â

A review of the antimicrobial activity of thermodynamically stable microemulsions

Microemulsions are thermodynamically stable, transparent, isotropic mixtures of oil, water and surfactant (and sometimes a co-surfactant), which have shown potential for widespread application in disinfection and self-preservation. This is thought to be due to an innate antimicrobial effect. It is suggested that the antimicrobial nature of microemulsions is the result of a combination of their inherent kinetic energy and their containing surfactants, which are known to aid the disruption of bacterial membranes. This review examines the contemporary evidence in support of this theory.</p

Development and evaluation of a novel, multifunctional, coprocessed excipient via roller compaction of α-Lactose Monohydrate and Magnesium Silicate

This study investigates co-processing lactose with synthetic amorphous magnesium silicate with the aim of expanding the use of directly compressible excipients based on native lactose. The co-processing was performed using roller compaction. The co-processed excipient was characterized using particle size analysis and compression properties (Kawakita equation). The co-processed excipient demonstrated plastic behavior upon compression, good flowability and crushing strength and a shorter disintegration time. Compatibility between the different ingredients of the co-processed excipient, as well as, between the co-processed excipient and model drugs was tested using Differential Scanning Calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The interaction between lactose and magnesium silicate proved to be of a physical nature. Formulating this co-processed excipient with Mebeverine HCl and Losartan Potassium as model drugs, indicated its suitability as a single multi-functional excipient. Co-processed lactose with magnesium silicate could be used as a single direct compression excipient for tablet manufacturing

Evaluation of Three Chitin Metal Silicate Co-Precipitates as a Potential Multifunctional Single Excipient in Tablet Formulations

The performance of the novel chitin metal silicate (CMS) co-precipitates as a single multifunctional excipient in tablet formulation using direct compression and wet granulation methods is evaluated. The neutral, acidic, and basic drugs Spironolactone (SPL), ibuprofen (IBU) and metronidazole (MET), respectively, were used as model drugs. Commercial Aldactone®, Fleximex® and Dumazole® tablets containing SPL, IBU and MET, respectively, and tablets made using Avicel® 200, were used in the study for comparison purposes. Tablets of acceptable crushing strength (>40 N) were obtained using CMS. The friability values for all tablets were well below the maximum 1% USP tolerance limit. CMS produced superdisintegrating tablets (disintegration time < 1 min) with the three model drugs. Regarding the dissolution rate, the sequence was as follow: CMS > Fleximex® > Avicel® 200, CMS > Avicel® 200 > Dumazole® and Aldactone® > Avicel® 200 > CMS for IBU, MET and SPL, respectively. Compressional properties of formulations were analyzed using density measurements and the compression Kawakita equation as assessment parameters. On the basis of DSC results, CMS co precipitates were found to be compatible with the tested drugs. Conclusively, the CMS co-precipitates have the potential to be used as filler, binder, and superdisintegrant, all-in-one, in the design of tablets by the direct compression as well as wet granulation methods

Development and Evaluation of a Novel, Multifunctional, Co-processed Excipient via Roll Compaction of α- Lactose Monohydrate and Magnesium Silicate

Abstract Co-processing of lactose with synthetic amorphous magnesium silicate has been investigated herein in the context of expanding native lactose applications as a direct compressible excipient. The foregoing was carried out using roll compactor. The obtained excipient was characterized using particle size analysis and compression properties (Kawakita equation). This new excipient showed plastic behavior upon compression, good flowability and crushing strength with shorter disintegration time. Compatibility was tested by differential scanning calorimetry (DSC) and FTIR. The interaction between lactose and Mg silicate proved to be of a physical nature. Formulation with this processed excipient on Mebeverine HCl and Losartan Potassium as model drugs indicated its suitability to be used as a single multifunctional excipient. As a result coprocessed lactose with Mg silicate can be used as a single direct compressible excipient for tablet manufacturing

Chitosan and Xanthan Gum Mixtures as Excipient for Controlled Release of Ambroxol HCl: In- vitro drug Release and Swelling Behavior

Abstract   Directly compressed matrices were produced using binary mixture of different chitosan (CH) and xanthan gum (XG) ratios. These hydrophilic excipients were used to control the release of ambroxol HCl. Three CH to XG ratios were investigated namely: 1:1, 1:4 and 4:1. Mucosolvan LA® was used as a reference commercial product.  The optimal CH to XG ratio was 1:1 and the optimal drug to polymer mixture ratio was 1:3. Matrix erosion, hydration and drug release study were carried out using a dissolution apparatus (basket method). The mechanism of release was discussed

Application of Excipient Made from Chitosan - Xanthan as a Single Component for the Controlled Release of Ambroxol Tablet

Abstract Oral controlled release (CR) matrix system of Ambroxol HCl was developed using binary hydrophilic polymer mixture of chitosan (CH) and xanthan gum (XG). Drug to polymer ratios (D: P) tested were 1:1 and 1:3 (w/w). The in-vitro drug release data was best fitted to Higuchi equation. The 1:1 ratio showed in-vitro dissolution similarity with the commercial product, Mucosolvan LA ®. The in-vivo release study was conducted on six volunteers.  The data showed that the D: P (1:1) ratio is bioequivalent to Mucosolvan  LA ® after the administration of a single oral dose under fasting conditions. Two in-vivo in-vitro correlations (IVIVC) were established between Cmax versus fraction of drug dissolved (FRD) after 4 h, and AUC versus ratio of fraction of drug dissolved (FRD) after 10 h where a multiple C level of IVIVC was obtained