Preparation and Evaluation of Phospholipid-Based Complex of Standardized Centella Extract (SCE) for the Enhanced Delivery of Phytoconstituents

In the present study, a phospholipid-based complex of standardized Centella extract (SCE) was developed with a goal of improving the bioavailability of its phytoconstituents. The SCE-phospholipid complex was prepared by solvent evaporation method and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy, and powder x-ray diffraction (PXRD) were used to confirm the formation of Centella naturosome (CN). The prepared complex was functionally evaluated by apparent solubility, in vitro drug release, ex vivo permeation, and in vivo efficacy studies. The prepared CN exhibited a significantly higher (12-fold) aqueous solubility (98.0 ± 1.4 μg/mL), compared to the pure SCE (8.12 ± 0.44 μg/mL), or the physical mixture of SCE and the phospholipid (13.6 ± 0.4 μg/mL). The in vitro dissolution studies revealed a significantly higher efficiency of CN in releasing the SCE (99.2 ± 4.7, % w/w) in comparison to the pure SCE (39.2 ± 2.3, % w/w), or the physical mixture (42.8 ± 2.09, % w/w). The ex vivo permeation studies with the everted intestine method showed that the prepared CN significantly improved the permeation of SCE (82.8 ± 3.7, % w/w), compared to the pure SCE (26.8 ± 2.4, % w/w), or the physical mixture (33.0 ± 2.7, % w/w). The in vivo efficacy studies using the Morris Water Maze test indicated a significant improvement of the spatial learning and memory in aged mice treated with CN. Thus, drug-phospholipid complexation appears to be a promising strategy to improve the aqueous solubility and bioavailability of bioactive phytoconstituents

Influence of the Component Excipients on the Quality and Functionality of a Transdermal Film Formulation

The influence of formulation variables, i.e., a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 and Eudragit® RS 100), on the physicochemical and functional properties of a transdermal film formulation was assessed. Several terpenes were initially evaluated for their drug permeation enhancement effects on the transdermal film formulations. d-Limonene was found to be the most efficient permeation enhancer among the tested terpenes. Transdermal film formulations containing granisetron (GRN) as a model drug, d-limonene as a permeation enhancer, and different ratios of a hydrophilic polymer (Methocel® E15) and a film-forming polymer (Eudragit® RL 100 or Eudragit® RS 100) were prepared. The prepared films were evaluated for their physicochemical properties such as weight variation, thickness, tensile strength, folding endurance, elongation (%), flatness, moisture content, moisture uptake, and the drug content uniformity. The films were also evaluated for the in vitro drug release and ex vivo drug permeation. The increasing ratios of Methocel®:Eudragit® polymers in the formulation linearly and significantly increased the moisture content, moisture uptake, water vapor transmission rate (WVTR), and the transdermal flux of GRN from the film formulations. Increasing levels of Methocel® in the formulations also increased the rate and extent of the GRN release and the GRN permeation from the prepared films

Influence of Carrier (Polymer) Type and Drug-Carrier Ratio in the Development of Amorphous Dispersions for Solubility and Permeability Enhancement of Ritonavir

The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs) of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3) SD showed a 36-fold higher ritonavir solubility compared to pure ritonavir. Similarly, ritonavir: Kolliphor® P188 (RP, 1:2) SD exhibited a 49-fold higher ritonavir solubility compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, up to a ritonavir: carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at ritonavir: Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supported the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3) and RP (1:2) were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %). A preliminary (six-month) stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that ritonavir solubility, dissolution, and permeability improvement can be achieved with a careful choice of the carrier polymer, and optimizing the amount of polymer in a SD formulation

Excipient Variability and Its Impact on Dosage Form Functionality

Pharmaceutical excipients are essential components of most modern dosage forms. Although defined as pharmacologically inert, excipients can be thought of as the true enablers of drug product performance. Unintentional variability in the properties of the excipients may be unavoidable, albeit minimizable. The variability may originate from the source, the excipient-manufacturing process, or during the manufacturing of dosage forms. Excipient variability may have a range of influences on their functionality and performance in the dosage form. A better understanding of these influences on the critical quality attributes of the final product is of prime importance. Modern analytical tools provide a significant assistance in characterizing excipient variability to achieve this understanding. The principles and concepts of Quality-by-Design, process analytical technology, and design space, provide a holistic risk-based approach toward manufacture and application of excipients in pharmaceutical formulations. The International Pharmaceutical Excipients Council (IPEC) has developed guidelines for proper selection, use, and evaluation of excipients in pharmaceutical products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association

Influence of carrier (polymer) type and drug-carrier ratio in the development of amorphous dispersions for solubility and permeability enhancement of ritonavir.

The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs) of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3) SD showed a 36-fold higher solubility of compared with pure ritonavir. Similarly, ritonavir:Kolliphor® P188 (RP, 1:2) SD exhibited a 49-fold higher solubility of ritonavir compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, upto a ritonavir:carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at a ritonavir:Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supporting the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3) and RP (1:2) were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %). A preliminary (six-month) stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that a good solubility, dissolution, and permeability improvement of ritonavir can be achieved with a careful choice of the carrier polymer, and by optimizing the amount of the chosen polymer in an SD formulation

Preparation and Evaluation of Phospholipid-Based Complex of Standardized Centella Extract (SCE) for the Enhanced Delivery of Phytoconstituents

In the present study, a phospholipid-based complex of standardized Centella extract (SCE) was developed with a goal of improving the bioavailability of its phytoconstituents. The SCE-phospholipid complex was prepared by solvent evaporation method and characterized for its physicochemical and functional properties. Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM), photomicroscopy, and powder x-ray diffraction (PXRD) were used to confirm the formation of Centella naturosome (CN). The prepared complex was functionally evaluated by apparent solubility, in vitro drug release, ex vivo permeation, and in vivo efficacy studies. The prepared CN exhibited a significantly higher (12-fold) aqueous solubility (98.0 ± 1.4 μg/mL), compared to the pure SCE (8.12 ± 0.44 μg/mL), or the physical mixture of SCE and the phospholipid (13.6 ± 0.4 μg/mL). The in vitro dissolution studies revealed a significantly higher efficiency of CN in releasing the SCE (99.2 ± 4.7, % w/w) in comparison to the pure SCE (39.2 ± 2.3, % w/w), or the physical mixture (42.8 ± 2.09, % w/w). The ex vivo permeation studies with the everted intestine method showed that the prepared CN significantly improved the permeation of SCE (82.8 ± 3.7, % w/w), compared to the pure SCE (26.8 ± 2.4, % w/w), or the physical mixture (33.0 ± 2.7, % w/w). The in vivo efficacy studies using the Morris Water Maze test indicated a significant improvement of the spatial learning and memory in aged mice treated with CN. Thus, drug-phospholipid complexation appears to be a promising strategy to improve the aqueous solubility and bioavailability of bioactive phytoconstituents

Influence of carrier (polymer) type and drug-carrier ratio in the development of amorphous dispersions for solubility and permeability enhancement of ritonavir.

The influence of the ratio of Eudragit® L100-55 or Kolliphor® P188 on the solubility, dissolution, and permeability of ritonavir was studied with a goal of preparing solid dispersions (SDs) of ritonavir. SDs were formulated using solvent evaporation or lyophilization techniques, and evaluated for their physical-chemical properties. The dissolution and permeability assessments of the functionality of the SDs were carried out. The preliminary functional stability of these formulations was assessed at accelerated storage conditions for a period of six months. Ritonavir: Eudragit® L100-55 (RE, 1:3) SD showed a 36-fold higher solubility of compared with pure ritonavir. Similarly, ritonavir:Kolliphor® P188 (RP, 1:2) SD exhibited a 49-fold higher solubility of ritonavir compared to pure ritonavir. Ritonavir dissolution from RE formulations increased with increasing ratios of Eudragit® L100-55, upto a ritonavir:carrier ratio of 1:3. The ritonavir dissolution from RP formulations was highest at a ritonavir:Kolliphor® P188 ratio of 1:2. Dissolution efficiencies of these formulations were found to be in line with, and supporting the dissolution results. The permeability of ritonavir across the biological membrane from the optimized formulations RE (1:3) and RP (1:2) were ~76 % and ~97 %, respectively; and were significantly higher compared to that of pure ritonavir (~20 %). A preliminary (six-month) stability study demonstrated the functional stability of prepared solid dispersions. The present study demonstrates that a good solubility, dissolution, and permeability improvement of ritonavir can be achieved with a careful choice of the carrier polymer, and by optimizing the amount of the chosen polymer in an SD formulation