The In Vitro Dissolution of Theophylline from Different Types of Hard Shell Capsules

ABSTRACT

The in vitro dissolution of theophylline from two-piece hard shell capsules has been investigated using different types of capsule shells (gelatin, gelatin/polyethylene glycol, hydroxypropyl methylcellulose), different formulations, different capsule fill weights, and different tamping forces. Analysis of variance confirmed that the formulation and the capsule shell materials were the most important factors influencing drug dissolution. The maximum extent of drug dissolution was significantly increased when hydroxypropyl methylcellulose (HPMC) capsules were used. The mean dissolution time (MDT) was significantly reduced, indicating a faster dissolution rate of the drug from HPMC capsules. The addition of microfine cellulose to the formulations as filler reduced the MDT in all cases, whereas the addition of lactose monohydrate did not enhance drug dissolution. The study confirmed that a change from gelatin hard shell capsules to gelatin/PEG or HPMC hard shell capsules should not pose problems with respect to drug absorption or bioavailability.     

Development and evaluation of dexibuprofen formulation with fast onset and prolonged effect

In the present study, in order to improve the solubility and bioavailability of poorly water-soluble dexibuprofen, a novel dexibuprofen-loaded solid dispersion was developed using the spray-drying technique. The controlled-release dexibuprofen formulation was developed by combining the immediate-release dispersion powder and the sustained-release formula. The solid dispersion composed of dexibuprofen/poloxamer 407/hydroxypropyl methylcellulose (HPMC) 2910 (50?cps)/sodium lauryl sulfate (SLS) (10/1/4/0.1?mg) was selected as the immediate-release formulation due to its increased solubility and dissolution rate. This immediate-release formulation showed a significantly higher initial plasma concentration, AUC, and C_max of dexibuprofen than those of dexibuprofen powder. Based on the prolonged effect of high plasma concentration, the formulation consisting of dexibuprofen/ethylcellulose/HPMC 2910 (4000?cps)/magnesium stearate (66/16.5/16.5/1?mg) was selected as the sustained-release formulation. Finally, the controlled-release (CR) formulation was prepared by encapsulating the immediate-release and sustained-release formulations in hard gelatin capsules. The proposed CR formulation showed enhanced AUC (5.5-fold) and C_max (3.5-fold) compared to dexibuprofen powder. The results of the present study suggest that the CR formulation containing dexibuprofen may be a potential oral dosage form for a fast onset and a prolonged effect of poorly water-soluble dexibuprofen.     

The in vitro dissolution of theophylline from different types of hard shell capsules

The in vitro dissolution of theophylline from two-piece hard shell capsules has been investigated using different types of capsule shells (gelatin, gelatin/polyethylene glycol, hydroxypropyl methylcellulose), different formulations, different capsule fill weights, and different tamping forces. Analysis of variance confirmed that the formulation and the capsule shell materials were the most important factors influencing drug dissolution. The maximum extent of drug dissolution was significantly increased when hydroxypropyl methylcellulose (HPMC) capsules were used. The mean dissolution time (MDT) was significantly reduced, indicating a faster dissolution rate of the drug from HPMC capsules. The addition of microfine cellulose to the formulations as filler reduced the MDT in all cases, whereas the addition of lactose monohydrate did not enhance drug dissolution. The study confirmed that a change from gelatin hard shell capsules to gelatin/PEG or HPMC hard shell capsules should not pose problems with respect to drug absorption or bioavailability.     

Enhancement of solubility and bioavailability of ambrisentan by solid dispersion using Daucus carota as a drug carrier: formulation,characterization, in vitro,and in vivo study

Ambrisentan is an US FDA approved drug, it is the second oral endothelin A receptor antagonist known for the treatment of pulmonary arterial hypertension, but its oral administration is limited due to its poor water solubility. Hence, the objective of the investigation was focused on enhancement of solubility and bioavailability of ambrisentan by solid dispersion technique using natural Daucus carota extract as drug carrier. Drug carrier was evaluated for solubility, swelling index, viscosity, angle of repose, hydration capacity, and acute toxicity test (LD₅₀). Ambrisentan was studied for the saturation solubility, phase solubility, and Gibbs free energy change. Compatibility of drug and the natural carrier was confirmed by DSC, FTIR, and XRD. Solid dispersions were evaluated for drug content, solubility, morphology, in vitro, and in vivo study. Screening of the natural carrier showed the desirable properties like water solubility, less swelling index, less viscosity, and acute toxicity study revealed no any clinical symptoms of toxicity. Drug and carrier interaction study confirmed the compatibility to consider its use in the formulation. Formed particles were found to be spherical with smooth surface. In vitro studies revealed higher drug release from the solid dispersion than that of the physical mixture. Bioavailability study confirms the increased absorption and bioavailability by oral administration of solid dispersion. Hence, it can be concluded that the natural Daucus carota extract can be the better alternative source for the preparation of solid dispersion and/or other dosage forms for improving solubility and bioavailability.     

Formulation and pharmacokinetics of gelucire solid dispersions of flurbiprofen

Context: Development of solid dispersions is to improve the therapeutic efficacy by increasing the drug solubility, dissolution rate, bioavailability as well as to attain rapid onset of action.

Objective: The present research deals with the development of solid dispersions of flurbiprofen which is poorly water soluble to improve the solubility and dissolution rate using gelucires.

Materials and methods: In this study, solid dispersions were prepared following solvent evaporation method using gelucire 44/14 and gelucire 50/13 as carriers in different ratios. Then the formulations were evaluated for different physical parameters, solubility studies, DSC, FTIR studies and in vitro dissolution studies to select the best formulation that shows rapid dissolution rate and finally subjected to pharmacokinetic studies.

Results and discussion: From the in vitro dissolution study, formulation F3 showed the better improvement in solubility and dissolution rate. From the pharmacokinetic evaluation, the control tablets produced peak plasma concentration (C_max) of 9140.84?±?614.36?ng/ml at 3?h T_max and solid dispersion tablets showed C_max?=?11?445.46?±?149.23?ng/ml at 2?h T_max. The area under the curve for the control and solid dispersion tablets was 31?495.16?±?619.92 and 43?126.52?±?688.89?ng h/ml and the mean resident time was 3.99 and 3.68?h, respectively.

Conclusion: From the above results, it is concluded that the formulation of gelucire 44/14 solid dispersions is able to improve the solubility, dissolution rate as well as the absorption rate of flurbiprofen than pure form of drug.     

Effect of casting solvent,film-forming agent and solubilizer on orodispersible films of a polymorphic poorly soluble drug: an in vitro/in silico study

Abstract

In the current work, a full factorial experimental design was utilized to formulate piroxicam into orodispersible films while investigating the effects of some formulation factors on the properties of the resulting films. These factors were (A) the casting solvent: water and acetone/water mixture; (B) the film-forming agent: HPMC K4M and Na-alginate; (C) the solubilization system: no solubilizer, L-arginine, poloxamer and L-arginine/poloxamer mixture. Sixteen formulation runs were prepared by solvent casting method to obtain 10?mg piroxicam dosage units. Drug particle size in the prepared formulations and dissolution efficiency at 30?min were selected as responses variables. Additionally, the prepared films from each formulation were evaluated for other characters as drug content, thickness, residual water…etc. A selected formulation was then evaluated for its in vivo disintegration, palatability and stability. Utilizing acetone in the casting solution, Na-alginate as film-forming agent or both of them resulted in formation of films with larger drug particles and slower dissolution. Combined use of L-arginine and poloxamer showed better drug dissolution than using each alone. HPMC was more favorable than Na-alginate regarding mechanical properties and moisture absorption. Films from the selected formulation showed fast in vivo disintegration and acceptable palatability. These films were stable for 6?months under accelerated storage conditions. According to the computer simulation using GastroPlus?, the in vitro/in vivo behavior of piroxicam in the tested formulation was similar to that of an immediate-release formulation containing BCS class I drug. The selected formulation is therefore would satisfy the WHO perquisites for applying the biowaiver.     

Evaluation of Solid Dispersions of Clofazimine

ABSTRACT

Clofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.     

Enhanced dissolution and bioavailability of grapefruit flavonoid Naringenin by solid dispersion utilizing fourth generation carrier

Context: Naringenin (NRG), the aglycone flavonoid present in grapefruits, possesses anti-inflammatory, anti-carcinogenic, anti-lipid peroxidation and hepato-protective effects. However, it is poorly soluble in water and exhibits slow dissolution after oral ingestion, thus restricting its therapeutic efficacy.

Objective: With the aim to enhance the dissolution rate and oral bioavailability of NRG, solid dispersion technique has been applied using Soluplus® as carrier.

Methods: Solid dispersions of NRG were prepared by solvent evaporation and kneading methods using various ratios (1:4, 3:7, 2:3 and 1:1) of NRG:Carrier. Characterization of the optimized formulations was performed using Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC) and X-ray diffraction (XRD) analysis. The in vivo behavior of the optimized formulations was also investigated in Wistar Albino rats.

Results: NRG solid dispersion showed a significantly higher solubility and drug dissolution rate than pure NRG (p?Conclusion: Based on these results, it was concluded that solid dispersion technique markedly enhances the in vitro drug release and in vivo behavior of the grapefruit flavonoid NRG.     

A novel osmotic pump-based controlled delivery system consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen: in vitro and in vivo evaluation

Abstract

In this study, a novel controlled release osmotic pump capsule consisting of pH-modulated solid dispersion for poorly soluble drug flurbiprofen (FP) was developed to improve the solubility and oral bioavailability of FP and to minimize the fluctuation of plasma concentration. The pH-modulated solid dispersion containing FP, Kollidon® 12 PF and Na₂CO₃ at a weight ratio of 1/4.5/0.02 was prepared using the solvent evaporation method. The osmotic pump capsule was assembled by semi-permeable capsule shell of cellulose acetate (CA) prepared by the perfusion method. Then, the solid dispersion, penetration enhancer, and suspending agents were tableted and filled into the capsule. Central composite design-response surface methodology was used to evaluate the influence of factors on the responses. A second-order polynomial model and a multiple linear model were fitted to correlation coefficient of drug release profile and ultimate cumulative release in 12?h, respectively. The actual response values were in good accordance with the predicted ones. The optimized formulation showed a complete drug delivery and zero-order release rate. Beagle dogs were used to be conducted in the pharmacokinetic study. The in vivo study indicated that the relative bioavailability of the novel osmotic pump system was 133.99% compared with the commercial preparation. The novel controlled delivery system with combination of pH-modulated solid dispersion and osmotic pump system is not only a promising strategy to improve the solubility and oral bioavailability of poorly soluble ionizable drugs but also an effective way to reduce dosing frequency and minimize the plasma fluctuation.     

Spray-dried solid dispersions containing ferulic acid: comparative analysis of three carriers,in vitro dissolution,antioxidant potential and in vivo anti-platelet effect

This article aimed to improve the relative solubility and dissolution rate of ferulic acid (FA) by the use of spray-dried solid dispersions (SDs) in order to ensure its in vitro antioxidant potential and to enhance its in vivo anti-platelet effect. These SDs were prepared by spray-drying at 10 and 20% of drug concentration using polyvinylpyrrolidone K30 (PVP-K30), polyethylene glycol 6000 (PEG 6000) and poloxamer-188 (PLX-188) as carriers. SDs and physical mixtures (PM) were characterized by SEM, XRPD, FTIR spectroscopy and TGA analysis. Spray-dried SDs containing FA were successfully obtained. Relative solubility of FA was improved with increasing carrier concentration. PVP-K30 and PEG 6000 formulations showed suitable drug content values close to 100%, whereas PLX-188 presented mean values between 70 and 90%. Agglomerates were observed depending on the carrier used. XRPD patterns and thermograms indicated that spray-drying led to drug amorphization and provided appropriate thermal stability, respectively. FTIR spectra demonstrated no remarkable interaction between carrier and drug for PEG 6000 and PLX-188 SDs. PVP-K30 formulations had changes in FTIR spectra, which denoted intermolecular O–H???O?=?C bonds. Spray-dried SDs played an important role in enhancing dissolution rate of FA when compared to pure drug. The free radical-scavenging assay confirmed that the antioxidant activity of PEG 6000 10% SDs was kept. This formulation also provided a statistically increased in vivo anti-platelet effect compared to pure drug. In summary, these formulations enhanced relative solubility and dissolution rate of FA and chosen formulation demonstrated suitable in vitro antioxidant activity and improved in vivo anti-platelet effect.     

Brain-targeted intranasal zaleplon solid dispersion in hydrophilic carrier system; 23 full-factorial design and in vivo determination of GABA neurotransmitter

Intranasal zaleplon solid dispersion was formulated to enhance the solubility, bioavailability and deliver an effective therapy. Zaleplon belongs to Class II drugs, and undergoes extensive first-pass metabolism after oral absorption exhibiting 30% bioavailability. A 2³ full-factorial design was chosen for the investigation of solid dispersion formulations. The effects of different variables include drug to carrier ratio (1:1 and 1:2), carrier type (polyethylene glycol 4000 and poloxamer 407), and preparation method (solvent evaporation and freeze drying) on different dissolution parameters were studied. The dependent variables determined from the in vitro characterization and their constraints were set as follows: minimum mean dissolution time, maximum dissolution efficiency and maximum percentage release. Numerical optimization was performed according to the constraints set based on the utilization of desirability functions. Differential scanning calorimetry, infrared spectroscopy, X-ray diffraction and scanning electron microscopy were performed. Ex vivo estimation of nasal cytotoxicity and assessment of the γ-aminobutyric acid level in plasma and brain 1?h after nasal SD administration in rabbits compared to the oral market product were conducted. The selected ZP-SD, with a desirability 0.9, composed of poloxamer 407 at drug to carrier ratio 1:2 successfully enhanced the bioavailability showing 44% increase in GABA concentration than the marketed tablets.     

Vitamin B12 buccoadhesive tablets: auspicious non-invasive substitute for intra muscular injection: formulation,in vitro and in vivo appraisal

Attempting to prepare a convenient bioavailable formulation of vitamin B₁₂ (cyanocobalamin), 17 tablet formulations were prepared by direct compression. Different concentrations of hydroxypropyl methyl cellulose (HPMC), carbopol 971p (CP971p), and chitosan (Cs) were used. The tablets were characterized for thickness, weight, drug content, hardness, friability, surface pH, in vitro drug release, and mucoadhesion. Kinetic analysis of the release data was conducted. Vitamin B₁₂ bioavailability from the optimized formulations was studied on rabbits by the aid of enzyme-linked immunosorbent assay. Neurotone^® I.M. injection was used for comparison. HPMC (F1-F4), CP971p (F5-F8), and HPMC/CP971p (F12-F15)-based formulations showed acceptable mechanical properties. The formulated tablets showed maximum swelling indices of 232?±?0.13. The surface pH values ranged from 5.3?±?0.03 to 6.6?±?0.02. Bioadhesive force ranged from 66?±?0.6 to 150?±?0.5?mN. Results showed that CP971p-based tablets had superior in vitro drug release, mechanical, and mucoadhesive properties. In vitro release date of selected formulations were fitted well to Peppas model. HPMC/CP971p-based formulations showed bioavailability up to 2.7-folds that of Neurotone^® I.M. injection.     

Evaluation of solid dispersions of Clofazimine

Clofazimine (CLF) was formulated with polyethylene glycol (PEG) and polyvinyl pyrrolidone (PVP) as a solid solid dispersion (SSD) to increase the aqueous solubility and dissolution rate of the drug. Different molecular weights of PEG (1500, 4000, 6000, and 9000 Da) and PVP (14,000 and 44,000 Da) were used in different drug:carrier weight ratios (1:1, 1:5, and 1:9) and their effect on the dissolution performance of the drug was evaluated in USP Type 2 apparatus using 0.1 N HCl medium. The dissolution rate was compared with corresponding physical mixtures, a currently marketed soft gelatin capsule product, and free CLF. The effect of different methods of preparation (solvent/melt) on the dissolution rate of CLF was evaluated for PEG solid dispersions. Saturation solubility and phase solubility studies were carried out to indicate drug:carrier interactions in liquid state. Infrared (IR) spectroscopy and X-ray diffraction (XRD) were used to indicate drug:carrier interactions in solid state. Improvement in the drug dissolution rate was observed in solid dispersion formulations as compared to the physical mixtures. The dissolution rate improved with the decreasing weight fraction of the drug in the formulation. Polyvinyl pyrrolidone solid dispersion systems gave a better drug release profile as compared to the corresponding PEG solid dispersions. The effect of molecular weight of the PEG polymers did not follow a definite trend, while PVP 14,000 gave a better dissolution profile as compared to PVP 44,000. Improvement in saturation solubility of the drug in the solid dispersion systems was noted in all cases. Further, IR spectroscopy indicated drug:carrier interactions in solid state in one case and XRD indicated reduction in the crystallinity of CLF in another. It was concluded that solid-dispersion formulations of Clofazimine can be used to design a solid dosage form of the drug, which would have significant advantages over the currently marketed soft gelatin capsule dosage form.     

Xanthan Gum and Alginate Based Controlled Release Theophylline Formulations

Abstract

The oral absorption of theophylline from two sustained release formulations, formulated using xanthan gum or sodium alginate, has been investigated in the beagle dog. A commercial product was used for comparison. Dissolution tests and an in vivo dog study both indicated that the xanthan gum tablet released drug at a constant rate and performed as a pH independent zero-order controlled release formulation. With the alginate tablet, faster dissolution rates were observed when acid medium was present. The pH dependent release behavior of the alginate formulation is explained. Drug release mechanisms which are influenced by the gel behaviors in these two polymers are discussed. The relative oral bioavailabilities of these two formulations in dog were 74–84% compared to immediately releasing capsules, and three-fold that of the commercial product with an equivalent dose.     

Novel cyclodextrin-based film formulation intended for buccal delivery of atenolol

Background: Unknown influence of cyclodextrin on the properties of the film formulation aimed for buccal application. Aim: Development and characterization of a novel bioadhesive film formulation for buccal atenolol delivery containing drug/cyclodextrin inclusion. Method: Interaction between atenolol and randomly methylated β-cyclodextrin (RAMEB) in solution was studied by phase solubility studies. The complex in solid state was prepared by the freeze-drying method and characterized by differential scanning calorimetry and Fourier-transformed infrared spectroscopy (FTIR). The drug, free or in complex form, was incorporated into polymeric films prepared by the casting method using ethylcellulose (EC), polyvinyl alcohol (PVA), and hydroxypropyl methylcellulose (HPMC). The prepared film formulations were characterized in terms of swelling, bioadhesion, and in vitro drug release. Results: The formation of a stabile inclusion complex (K_s = 783.4?±?21.6 M^?1) in 1:1 molar stoichiometry was confirmed in solution and in solid state. The swelling properties of films were predominated by the type of polymer used in the formulation. In vitro bioadhesive properties of the films were well correlated with the swelling properties of the polymers used in the formulation. Although incorporation of the drug, free or in complex form, decreased the bioadhesion of the films, PVA- and HPMC-based formulations retained suitable bioadhesive properties. Higher atenolol solubility upon complexation with RAMEB increased the drug dissolution rate under conditions designed to be similar to those on the buccal mucosa, but it has decreased the drug release rate from the PVA and HPMC film formulation, leading to a sustained drug release pattern. In the case of EC-based films, RAMEB promoted drug release. Other parameters that influenced the drug release rate were associated with the structure of the polymer used in the formulation, swelling characteristics of the films, and the interaction between atenolol and hydrophilic polymers that was demonstrated by FTIR analysis. Conclusion: Incorporation of atenolol in the form of an inclusion complex into hydrophilic films may be an appropriate strategy to prepare a suitable formulation for buccal drug delivery.     

Physical and chemical characterization of thermosoftened bases for molten filled hard gelatin capsule formulations

Abstract

Dynafill, Dynasan-114, Lutrol-F68, PEG-10000 and PEG-20000 have been examined as potential bases for the preparation of fusion formed solid dispersions for molten filling into hard gelatin capsules. Investigations included, an examination of thermal effects on crystal structure by DSC and XRD, a theological study to evaluate capsule filling characteristics, dissolution studies on drug/base formulations, chemical analysis for free fatty acid impurities in Dynafill and Dynasan-114, and detailed studies on selected drug/base formulations. PEG-20000 and Dynasan-114 were not examined in detail, after preliminary investigations had shown high viscosity and poor filling characteristics for PEG-20000 and poor dissolution characteristics for Dynasan-114. Dynafill provided good release profiles when formulated with a variety of model drugs (Acetohexamide, Ibuprofen, Indomethacin, Quinidine sulphate and Theophylline). Results from hot stage photomicrography supported by DSC and XRD were used to construct a phase diagram of the Ibuprofen/Lutrol-F68 system. The evidence from the phase diagram indicated the formulation of a simple eutectic system with no solid solubility and a eutectic composition at approximately 35% w/w Ibuprofen.     

Preparation,release and pharmacokinetics of a risperidone elementary osmotic pump system

Preparation and in vitro/in vivo evaluation of risperidone elementary osmotic pump (RIS-EOP) formulations were investigated. A method for the preparation of RIS-EOP tablets was developed by modulating RIS solubility with citric acid. The influence of osmotic agents and the compositions of semipermeable membrane on drug release profiles was evaluated. The formulation of RIS-EOP was optimized by orthogonal design. The in vitro release profile of the optimum formulation achieved to deliver RIS at an approximate zero-order up to 12?h. The pharmacokinetic profiles of RIS-EOP were evaluated compared with immediate release tablets in beagle dogs. The mean t_max and mean residence time of RIS-EOP for RIS and its active metabolite, 9-hydroxyrisperidone, were remarkably longer, compared with immediate release tablets. These results corroborated prolonged release of RIS from EOP formulations. Moreover, drug plasma levels with lower fluctuations could be achieved with RIS-EOP tablets. These results suggested that increasing drug solubility by adding or reacting with alkali/acid might be used for the preparation of EOP tablets of certain poorly water-soluble drugs.     

Formulation and optimization of spray-dried amlodipine solid dispersion for enhanced oral absorption

Objective: To enhance the oral absorption of photosensitive amlodipine free base, which exhibits a slow dissolution rate and low permeability characteristics, an amorphous solid dispersion system was formulated and characterized.

Material and methods: The solid dispersion was prepared by dispersing the amlodipine free base in excess dextrin (1:10 by weight) using a spray-drying technique in the presence of a minimum amount (0.9% w/w) of SLS as an absorption enhancer. The dextrin-based solid dispersion of amlodipine (Amlo-SD) was evaluated in term of formulation, characterization and in vivo absorption study, as well as the spray-drying process was also optimized.

Results and discussion: The Amlo-SD particles were spherical with a smooth surface and an average particle size of 12.9 μm. Amlodipine was dispersed in an amorphous state and its content remained uniform in the Amlo-SD. The physicochemical stability of the Amlo-SD was maintained at room temperature for 6 months and the photostability was considerably improved. The dissolution of the Amlo-SD was much faster than that of amlodipine at pH 1.2 and 6.8. Amlo-SD produced significantly higher plasma concentrations of amlodipine in rats than amlodipine alone. Amlo-SD with and without SLS provided 2.8- and 2.0-fold increase in AUC, respectively: the difference seems to be attributed to a permeability enhancement effect by SLS.

Conclusion: The Amlo-SD with SLS system is a potential formulation option for amlodipine.     

Formulation development and in vitro evaluation of solidified self-microemulsion in the form of tablet containing atorvastatin calcium

Aim: The objective of our present study was to prepare solid self-microemulsion in the form of tablet of a poorly water soluble drug, Atorvastatin calcium (ATNC) to increase the solubility, dissolution rate, and minimize the hazards experienced from liquid emulsions.

Materials and methods: Self-microemulsifying ATNC tablet was formulated mainly by using self-emulsifying base, solidifying agent silicon dioxide and sodium starch glycolate as tablet disintegrant. Self-emulsifying base containing Transcutol P, Gelucire 44/14, and Lutrol F68 with their ratios in the formulation, were best selected by solubility study and ternary phase diagram in different vehicles. Particle size of microemulsion from tablet, physical parameters of the tablet and drug content has been checked. In vitro drug release rate has been carried out in phosphate buffer medium (pH 6.8). Physicochemical characterization of the drug in the optimized formulation has been performed to check drug-excipient incompatibility, if any.

Results: Average particle diameter of the emulsions formed from the tablet was found to be below 100?nm in case of formulation F4 and F5, which indicated microemulsions has been formed. In vitro drug release from the formulations F3, F4, and F5 was found to be >90%, indicated the enhancement of solubility of ATNC compared to parent drug. Differential thermal analysis (DTA), Powder X-ray Diffraction (X-RD) and Fourier transform infra red (FTIR) study proved the identity of the drug in the optimized formulation.

Conclusion: The tablet form of self-microemulsifying (SME) drug delivery is good for solubility enhancement.     

New ethanol and propylene glycol free gel formulations containing a minoxidil-methyl-β-cyclodextrin complex as promising tools for alopecia treatment

New topical totally aqueous formulations that improve the low water solubility of minoxidil and realize an adequate permeability of drug in the skin are proposed. These formulations are lacking in propylene glycol and alcohol that are the principal irritant ingredients present in minoxidil commercial solutions. In order to enhance poor water solubility of minoxidil randomly methyl-β-cyclodextrin was used, and four hydrogels such as, calcium alginate, sodium alginate, carbopol 934 and hydroxyethylcellulose were utilized to ensure a prolonged time of contact with the scalp. The inclusion complex minoxidil/methyl-β-cyclodextrin with a molar ratio 1:1 was obtained by freeze drying and evaluated by NMR, FT-IR and DSC analysis. An apparent stability constant of formed inclusion complex was calculated by phase solubility diagram and its value was 400?M^?1. The solid inclusion complex was used to prepare gel formulations with similar dose to minoxidil commercial solution. The gels were evaluated for various technological parameters including rheological behavior, in vitro drug release and ex vivo permeation through pig skin. The best performance was observed for the calcium alginate formulation.