A. W. Malick

Self-emulsifying drug delivery systems (SEDDS) with polyglycolyzed glycerides for improving in vitro dissolution and oral absorption of lipophilic drugs

Abstract The ability of polyglycolyzed glycerides (PGG) with varying fatty acid and polyethylene glycol (PEG) chain lengths to produce the self-emulsification of oil in water has been investigated. The quality of the resulting emulsions depends on the oil and emulsifier pair selected. These self-emulsifying drug delivery systems (SEDDS) were prepared using various concentrations of PGG as emulsifiers. Two oils, a medium-chain triglyceride (Neobee M5) and Peanut Oil, were chosen as the vehicle for the drug. A lipophilic drug with excellent oil solubility was selected for this study. The droplet size distribution, the release rate of the drug and the oil/water partition coefficient (PC o/w ) of the drug in these systems were evaluated for the SEDDS obtained. The results indicate that PGG are effective emulsifiers for SEDDS. Droplet particle size in combination with droplet polarity in the emulsion are prerequisites for efficient SEDDS. The PC o/w of the drug from these SEDDS is helpful in evaluating these properties. A phase diagram was used to obtain the optimum concentrations of drug, oil and emulsifying agent. The results obtained with PGG were compared with previously reported SEDDS for the efficiency of drug release (Bachynsky et al., (1989) AAPS Annual Meeting). In vitro dissolution and in vivo absorption of a lipophilic drug from SEDDS are compared with those properties of other dosage forms.

Controlled-Release Drug Delivery Systems for Prolonged Gastric Residence: An Overview

(1996). Controlled-Release Drug Delivery Systems for Prolonged Gastric Residence: An Overview. Drug Development and Industrial Pharmacy: Vol. 22, No. 6, pp. 531-539.

Physical and enteric properties of soft gelatin capsules coated with eudragit ® L 30 D-55

Abstract The enteric coating of soft gelatin capsules (SGC) containing ibuprofen in either PEG 400 or Miglyol© was investigated. The effects of two plasticizers, triethyl citrate (TEC) and tributyl citrate (TBC), on the physical and enteric properties of SGC coated with Eudragit ® L 30 D-55 were studied. The water soluble plasticizer TEC was found to be a good plasticizing agent for the Eudragit® L 30 D-55 irrespective of the fill liquid, while the TBC provided satisfactory results only for capsules containing the hydrophobic fill liquid, Miglyol ®. The combination of TEC and TBC provided effective plasticization for the acrylic coating regardless of the fill liquid. A subcoat of HPMC showed no effect on the enteric protection of either Miglyol® - and PEG-containing capsules that were stored at room temperature and zero percent relative humidity. The moisture content of the gelatin shell of the film coated SGC stored at room temperature and at 0 or 96% relative humidity was followed as a function of time. The load strength of the capsules was measured during 3 months of storage using an Instron universal testing apparatus, and the physical-mechanical properties of the capsules were correlated with the moisture content of the SGC. As the moisture content of the gelatin decreased, all formulations exhibited an increase in load strength.

Release performance of a poorly soluble drug from a novel, Eudragit-based multi-unit erosion matrix.

Mechanisms governing the release of drugs from controlled delivery systems are mainly diffusion, osmosis and erosion. For poorly soluble drugs, the existing mechanisms are limited to osmosis and matrix erosion, that are commonly observed in single unit matrix dosage forms. This study reports formulation and dissolution performance of Eudragit L 100 55 and Eudragit S 100 based multi-unit controlled release system of a poorly soluble thiazole based leukotriene D(4) antagonist, that was obtained by an extrusion/spheronization technique. Effect of triethyl citrate, that was incorporated in the matrix, on the dissolution performance of the drug was also evaluated. In vitro matrix erosion and drug release from the pellets were determined by the use of USP Dissolution Apparatus I, pH 6.8 phosphate buffer, gravimetry and UV spectrophotometry, respectively. Results obtained demonstrated that matrix erosion and drug release occurred simultaneously from the pellets. Pellets eroded with a consequent reduction in size without any change in the pellet geometry for over 12 h. Matrix erosion and drug release followed zero order kinetics. Data obtained strongly suggested a polymer controlled, surface erosion mechanism.

Factors affecting the efficiency of a self-emulsifying oral delivery system

AbstractDosage forms containing a self-emulsifying system have shown significant promise in improving the in vitro dissolution rate and oral absorption of lipophilic drugs. In such a system, a surfactant, or a surfactant plus medium chain monoglyceride (co-emulsifier), is added to a lipophilic vehicle (oil) containing dissolved drug. In the present study, surfactants with different hydrophile-lipophile balance (HLB), fatty acid glycerides (co-emulsifiers) with varying fatty acid (C8-C18) chain length, and lipophilic vehicles (oils) containing different fatty acid (C8-C18) compositions were evaluated for their effectiveness in producing self-emulsifying systems. nis investigation showed that the HLB of the surfactant, as well as the fatty acid chain length of the monoglyceride have a significant effect on the performance of the self-emulsifying system; a surfactant with an HLB in the range of 10–15 and a monoglyceride of medium chain fatty acid (C8-C10) were most effective. Also, there are certain critical...

Physical-mechanical properties of film-coated soft gelatin capsules

Abstract Soft gelatin capsules containing ibuprofen dissolved in either PEG 400 or Miglyol® 812 were coated with an aqueous dispersion of Eudragit® L 30 D-55 using a Mini Hi-Coater. The physical-mechanical properties of the coated capsules, including tensile strength, Youngs modulus and tensile toughness, were determined using a Chatillon DFGS50 force gauge attached to a Chatillon TCD-200 motorized test stand. The diametral compression tests were conducted at a rate of 12.7 mm/minute. Force-deflection curves were obtained and mathematically manipulated to yield stress-strain diagrams. The influence of two plasticizing agents, triethyl citrate (TEC) and tributyl citrate (TBC), on the physical-mechanical properties was determined. The hydrophilic plasticizer TEC was found to be the best plasticizer for the acrylic films, regardless of the fill liquid. The physical-mechanical properties of the coated and uncoated soft gelatin capsules were a function of the fill liquid. Temperature and humidity were found to influence the physical-mechanical properties of the coated capsules. The adhesion between the gelatin capsule and the acrylic polymer was found to be dependent on both the fill liquid and plasticizer in the coating formulation. Coating dispersions plasticized with TEC exhibited good adhesion with both the PEG 400 and the Miglyol® 812, whereas the TBC plasticized film coating showed good adhesion with the Miglyol® 812 fill liquid. The acrylic film coatings for the PEG-containing capsules and plasticized with TBC exhibited an increased adhesion of the polymer to substrate over time when stored at both high temperature and high humidity.

Evaluation of Two New Tablet Lubricants -Sodium Stearyl Fumarate and Glyceryl Behenate. Measurement of Physical Parameters (Compaction, Ejection and Residual Forces) in the Tableting Process and the Effect on the Dissolution Rate

AbstractA comparison of two new tablet lubricants, sodium stearyl fumarate and glyceryl behenate, was made with magnesium stearate. Physical parameters such as compaction force, ejection force and residual force were investigated and quantified. The effect of these lubricants on a biopharmaceutical parameter such as dissolution rate was also evaluated. The results indicate that where magnesium stearate cannot be used due to problems of compaction, lubrication, stability or for biopharmaceutical reasons, sodium stearyl fumarate should be used as the tablet lubricant of choice, followed by glyceryl behenate as the next alternative

Compaction Properties of Spheronized Binary Granular Mixtures

AbstractTwo spheronized granular formulations containing 20% anhydrous lactose/80% microcrystalline cellulose (MCC) and 80% anhydrous lactose/20% microcrystalline cellulose were blended in various proportions and compressed. Physical-mechanical properties of the resulting compacts were investigated using tableting indices and compared with powder mixtures of the same compositions. The compacts were compressed at a solid fraction of 0.80 for both powder and bead mixtures. An additional set of bead compacts were made at a solid fraction of 0.87. The thickness of the compacts was measured in the post-ejection stage to investigate their expansion behavior. The tensile strength with and without a stress concentrator and the dynamic indentation hardness of the compacts were determined. The brittle fracture index (BFI) and bonding index (BI) values were also calculated. The microstructure of the beads and compacts were investigated using scanning electron microscopy to observe the bonding phenomena. The results ...

The Impact of Hot Melt Extrusion and Spray Drying on Mechanical Properties and Tableting Indices of Materials Used in Pharmaceutical Development

The impact of melt extrusion (HME) and spray drying (SD) on mechanical properties of hypromellose acetate succinate (HPMCAS), copovidone, and their formulated blends was studied and compared with that of reference excipients. Tensile strength (TS), compression pressure (CP), elastic modulus (E), and dynamic hardness (Hd ) were determined along with Hiestand indices using compacts prepared at a solid fraction of ∼0.85. HPMCAS and copovidone exhibited lower Hd , lower CP, and lower E than the reference excipients and moderate TS. HPMCAS was found to be highly brittle based on brittle fracture index values. The CP was 24% and 61% higher for HPMCAS after SD and HME, respectively, than for unprocessed material along with a higher Hd . Furthermore, the TS of HPMCAS and copovidone decreased upon HME. Upon blending melt-extruded HPMCAS with plastic materials such as microcrystalline cellulose, the TS increased. These results suggest that SD and HME could impact reworkability by reducing deformation of materials and in case of HME, likely by increasing density due to heating and shear stress in a screw extruder. A somewhat similar effect was observed for the dynamic binding index (BId ) of the excipients and formulated blends. Such data can be used to quantitate the impact of processing on mechanical properties of materials during tablet formulation development.

Stability of a hydrophobic drug in presence of hydrous and anhydrous lactose.

The chemical stability of a hydrophobic Leukotriene receptor antagonist drug was investigated in the presence of lactose (both hydrous and anhydrous) under various humidity and temperature conditions. The effect of wet-granulation and direct-mixing on the stability of the drug was also studied. Mixtures of drug:lactose in the ratio 1:25, 1:50 and 1:100 were prepared and analyzed over a 6 week period after storage at 40, 83 and 97% RH (all at 25 degreesC) and 75% RH at 40 degreesC. The mixtures were subjected to LOD, Karl--Fischer titrimetry, HPLC and DSC analysis to evaluate the amount of moisture pickup, percent potency and presence of drug-moisture-lactose interaction. Mixtures containing lactose anhydrous picked up more moisture and exhibited greater drug degradation than those containing lactose hydrous. Also, mixtures stored under high temperature and humidity condition showed greater moisture uptake than those stored at high humidity alone. Lactose anhydrous becomes hydrated on exposure to high humidity/temperature and storage conditions. The transition state of lactose and not its stable state may be responsible for its greater interaction and subsequent degradation of the drug. Therefore, the normal belief that lactose anhydrous, which has less than 0.5% moisture, should provide greater stability as compared to lactose hydrous, needs to be properly evaluated.