Development and in vitro evaluation of a buccal drug delivery system based on preactivated thiolated pectin

The aim of this study was to evaluate the potential of preactivated thiolated pectin (Pec-Cys-MNA) for buccal drug delivery. Therefore, a gel formulation containing this novel polymer and the model drug lidocaine was prepared and investigated in vitro in terms of rheology, mucoadhesion, swelling behavior and drug release in comparison to formulations based on pectin (Pec) and thiolated pectin (Pec-Cys). Both pectin derivatives showed gel formation without addition of any other excipient due to self-crosslinking thiol groups. Under same conditions, pectin did not show gel formation. Viscosity of Pec-Cys-based formulation increased 92-fold and viscosity of Pec-Cys-MNA-based formulations by 4958-fold compared to pectin-based formulation. Gels did not dissolve in aqueous environment during several hours and were able to take up water. Mucoadhesion of pectin on buccal tissue could be improved significantly, value of total work of adhesion increased in the following rank order: Pec-Cys-MNA?>?Pec-Cys?>?Pec. The retention time of a model drug incorporated in gel formulations on buccal mucosa under continuous rinsing with phosphate-buffered saline was prolonged, after 1.5?h 3-fold higher amount of a model drug was to be found on tissue after application of Pec-Cys-MNA-based formulation compared to pectin-based and 2-fold compared to Pec-Cys-based formulation. The Pec-Cys-MNA-based gel showed a more sustained release of lidocaine than Pec-Cys-based gel, whereas pectin solution revealed an immediate release. According to these results, the self-crosslinking pectin-derivative is a promising tool for buccal application.     

Preparation and in vivo evaluation of spray dried matrix type controlled-release microparticles of tamsulosin hydrochloride for orally disintegrating tablet

The objective of this study was to achieve an optimal formulation of spray dried matrix type controlled-release (MTCR) microparticles containing tamsulosin hydrochloride for orally disintegrating tablet. To control the release rate of tamsulosin hydrochloride, Acrylate-methacrylate copolymer (Eudragit^® L-100 or Eudragit^® S-100) and ethylcellulose were employed on the composition of MTCR microparticles. Physicochemical properties of MTCR microparticles such as particle size and SEM were characterized. Pharmacokinetic parameters of tamsulosin hydrochloride were evaluated in the rats after oral administration. MTCR microparticles were spherical microparticles of around 10 µm diameter with a corrugated surface. ODTs containing MTCR microparticles were disintegrated within 30 s and MTCR microparticles were able to control the release rate of tamsulosin hydrochloride following Fickian diffusion mechanism. The in vitro release rates of tamsulosin hydrochloride from MTCR microparticles were proportional to the ratio of Acrylate-methacrylate copolymer to ethylcellulose. Moreover, MTCR microparticles retarded the in vivo release rate of tamsulosin hydrochloride without reducing the bioavailability. Our results suggest that MTCR microparticles may be potential oral dosage forms to control the release and to improve the bioavailability of tamsulosin hydrochloride.     

Evaluation of performance of co crystals of mefloquine hydrochloride in tablet dosage form

Objective: The objective of present investigation was to evaluate performance of cocrystals of Mefloquine Hydrochloride (MFL) in tablet dosage form. Our previous investigation showed significant effect of cocrystal formers on improving the solubility and dissolution rate of Mefloquine hydrochloride by cocrystallization method when prepared by solution cocrystallization method.

Materials and methods: Prepared cocrystals of MFL with different ratio of cocrystal formers were incorporated in tablet dosage form and evaluated for micrometric properties, drug content, hardness, disintegration test, vitro dissolution studies and stability studies. Performance was compared with laboratory prepared tablet of MFL 250 mg.

Results: The considerable improvement in the dissolution rate was observed in case of cocrystals based tablets than pure MFL tablets.

Discussion and conclusion: So we can incorporate cocrystals in tablet dosage form to enhance in vitro and in vivo performance. To the best of our knowledge, this is the first report, cocrystals has been evaluated in tablet dosage form.     

Development and in vitro evaluation of diltiazem hydrochloride transdermal patches based on povidone-ethylcellulose matrices

To select a suitable formulation for the development of transdermal drug-delivery system of diltiazem hydrochloride. Transdermal patches of the drug, employing different ratios of polymers, ethylcellulose (EC), and povidone (PVP) were developed and evaluated for the potential drug delivery using depilated freshly excised abdominal mouse skin. The influence of different film compositions on in vitro drug permeation into receptor fluid were studied using a modified Franz diffusion cell. The cumulative amount of drug was found to be proportional to the square root of time, i.e., Higuchi kinetics. From this study, it was concluded that the films composed of povidone:ethylcellulose (1:2) should be selected for the development of transdermal drug-delivery system of diltiazem hydrochloride, using a suitable adhesive layer and backing membrane, for potential therapeutic use.     

Formulation and evaluation of floating tablet of H2-receptor antagonist

Context: Conventional sustained dosage form of ranitidine hydrochloride (HCl) does not prevent frequent administration due to its degradation in colonic media and limited absorption in the upper part of GIT.

Objectives: Ranitidine HCl floating tablet was formulated with sublimation method to overcome the stated problem.

Methods: Compatibility study for screening potential excipients was carried out using Fourier transform infrared spectroscopy (FT-IR) and differential scanning chromatography (DSC). Selected excipients were further evaluated for optimizing the formulation. Preliminary screening of binder, polymer and sublimating material was based on hardness and drug release, drug release with release kinetics and floating lag time with total floatation time, respectively. Selected excipients were subjected to 3² factorial design with polymer and sublimating material as independent factors. Matrix tablets were obtained by using 16/32” flat-faced beveled edges punches followed by sublimation.

Results: FT-IR and DSC indicated no significant incompatibility with selected excipients. Klucel-LF, POLYOX WSR N 60?K and l-menthol were selected as binder, polymer and sublimating material, respectively, for factorial design batches after preliminary screening. From the factorial design batches, optimum concentration to release the drug within 12?h was found to be 420?mg of POLYOX and 40?mg of l-menthol. Stability studies indicated the formulation as stable.

Conclusion: Ranitidine HCl matrix floating tablets were formulated to release 90% of drug in stomach within 12?h. Hence, release of the drug could be sustained within narrow absorption site. Moreover, the dosage form was found to be floating within a fraction of second independent of the pH of media ensuring a robust formulation.     

Mucoadhesive dosage form of lidocaine hydrochloride: I. Mucoadhesive and physicochemical characterization

The aim of this study was to characterize a buccal mucoadhesive film using lidocaine and its hydrochloride salt (LDHCL) as a model drug. Buccal films were developed using carbopol 971P as a mucoadhesive polymer, and glycerol as a plasticizer. Scanning Electron Microscope, Differential Scanning Calorimetry, X-ray powder diffraction, and Fourier Transform Infra Red techniques were used to characterize the mucoadhesive films. Bioadhesive properties were evaluated using the Universal Instron Instrument with chicken pouch as a model tissue.

LDHCL and its base were present in carbopol 971P films in a molecular dispersion state without exerting any effect on the glass transition of these films. The mucoadhesive force between the chicken pouches and the film containing glycerol did not change by time during the tested period (1-20 min), while increased with increasing the amount of glycerol (10-40% w/w of polymer content). Furthermore, a linear increase in the mucoadhesive force was accompanied by the increase in the film thickness, while a linear decrease followed by plateau was obtained when loading the patch with LDHCL at concentration above 1 mg/cm².

Loading carbopol film with lidocaine base, in a concentration up to 6 mg/cm² decreased linearly the mucoadhesive properties, which could be attributed to salt formation between the acidic carboxylic moiety of carbopol and basic lidocaine.     

Dual-purpose vardenafil hydrochloride/dapoxetine hydrochloride orodispersible tablets: in vitro formulation/evaluation,stability study and in vivo comparative pharmacokinetic study in healthy human subjects

Erectile dysfunction (ED) is the most important disorder after premature ejaculation for sexual activity in men. Vardenafil hydrochloride (VH) is an oral therapy for the treatment of erectile dysfunction. VH oral disintegrating tablets (ODTs) have been prepared by freeze drying technique to improve its dissolution profile and the overall clinical performance. Dapoxetine hydrochloride (DH) was added to the best three formulae of the prepared VH ODTs to treat premature ejaculation. All the ODTs formulae were evaluated for weight variation, friability, drug content, in vitro disintegration time, wetting time, and the dissolution study. Gelatin as a matrix former with N-methylpyrrolidone as a solubilizer in VH/DH ODTs improved the dissolution rate and extent of release of VH and DH with 100% of drug being dissolved after 15?min. In vivo study results from six healthy male volunteers showed shorter T_max of VH from VH/DH ODT of 0.583?±?0.129?h and shorter T_max of DH from VH/DH ODT of 0.625?±?0.137?h and showed AUC_0–12 of VH from VH/DH ODT of 39.234?±?10.932?ng/ml^?h¹ and AUC_0–12 of DH from VH/DH ODT of 531.681?±?129.544?ng/ml^?h¹, with relative bioavailability values of 100.9 and 85%, respectively, compared to (Levitra^®) and (Priligy^®).     

Effective manipulation for industrial robot manipulators based on tablet PC

Along with the progress in robot technologies, industrial robot manipulators nowadays have applied for more diverse and complex tasks. Consequently, the conventional manipulative devices, such as the teaching pendant and keyboard, become less suitable for task governing and teaching. Motivated by it, in this paper, we propose a novel manipulation system for industrial robot manipulators based on a tablet PC. With wireless communication, the proposed system provides flexibility for remote manipulation. Furthermore, a graphical interface and several assistive tools are developed, allowing the operator to conduct tasks in a more intuitive way. Experiments are executed to demonstrate the effectiveness of the proposed manipulation system, with its performance compared to conventional manipulative devices.     

Development of topical hydrogels of terbinafine hydrochloride and evaluation of their antifungal activity

The purpose of this study was to prepare hydrogels and microemulsion (ME)-based gel formulations containing 1% terbinafine hydrochloride (TER-HCL) and to evaluate the use of these formulations for the antifungal treatment of fungal infections. Three different hydrogel formulations were prepared using chitosan, Carbopol® 974 and Natrosol® 250 polymers. A pseudo-ternary phase diagram was constructed, and starting from ME formulation, a ME gel form containing 1% Carbopol 974 was prepared. We also examined the characteristic properties of the prepared hyrogels. The physical stability of hydrogels and the ME -based gels were evaluated after storage at different temperatures for a period of 3 months. The release of TER-HCL from the gels and the commercial product (Lamisil®) was carried out by using a standard dialysis membrane in phosphate buffer (pH 5.2) at 32?°C. The results of the in vitro release study showed that the Natrosol gel released the highest amount of drug, followed by Carbopol gel, chitosan gel, commercial product, and the microoemulsion-based gel in that order. In vitro examination of antifungal activity revealed that all the prepared and commercial products were effective against Candida parapsilosis, Penicillium, Aspergillus niger and Microsporum. These results indicate that the Natrosol®-based hydrogel is a good candidate for the topical delivery of TER-HCL.     

Design,characterization and ex vivo evaluation of chitosan film integrating of insulin nanoparticles composed of thiolated chitosan derivative for buccal delivery of insulin

The purpose of this study is to optimize and characterize of chitosan buccal film for delivery of insulin nanoparticles that were prepared from thiolated dimethyl ethyl chitosan (DMEC-Cys). Insulin nanoparticles composed of chitosan and dimethyl ethyl chitosan (DMEC) were also prepared as control groups. The release of insulin from nanoparticles was studied in vitro in phosphate buffer solution (PBS) pH 7.4. Optimization of chitosan buccal films has been carried out by central composite design (CCD) response surface methodology. Independent variables were different amounts of chitosan and glycerol as mucoadhesive polymer and plasticizer, respectively. Tensile strength and bioadhesion force were considered as dependent variables. Ex vivo study was performed on excised rabbit buccal mucosa. Optimized insulin nanoparticles were obtained with acceptable physicochemical properties. In vitro release profile of insulin nanoparticles revealed that the highest solubility of nanoparticles in aqueous media is related to DMEC-Cys nanoparticles. CCD showed that optimized buccal film containing 4% chitosan and 10% glycerol has 5.81?kg/mm² tensile strength and 2.47?N bioadhesion forces. Results of ex vivo study demonstrated that permeation of insulin nanoparticles through rabbit buccal mucosa is 17.1, 67.89 and 97.18% for chitosan, DMEC and DMEC-Cys nanoparticles, respectively. Thus, this study suggests that DMEC-Cys can act as a potential enhancer for buccal delivery of insulin.     

Cubosomal based oral tablet for controlled drug delivery of telmisartan: formulation,in-vitro evaluation and in-vivo comparative pharmacokinetic study in rabbits

A nanoparticulate system; cubosomes has been suggested to support the controlled release of Telmisartan (TEL), a poorly water-soluble medication. Four distinctive formulae were selected according to the results of three estimated responses. The liquid cubosomes were successfully adsorbed onto Aerosil 380 to form granules. The formulae were evaluated for their flow properties. The best granules were compressed into tablets suitable for oral administration. The tablets were evaluated for its performance. The in vivo study of the best selected cubosomal tablets was checked after oral administration in the blood of albino rabbits utilizing an HPLC method. Results revealed that the highest EE was shown in formulae C5 (59.68?±?1.3). All the prepared formulae had particle size less than 500?nm with PDI < 0.5 and the highest zeta potential results were observed in C5, C7, C9, C11 and C12 (>30?mv). A7 and A9 prepared using Aerosil 380 showed a perfect flowability. After 1?h of dissolution testing, the commercial product showed a 66% drug release while the release of all cubosomal formulae didn’t exceed 35% during the first hour reaching a 85% of the drug released at the end of 24?h. A7 was selected for the in vivo study; T_max of TEL absorption is increased for cubosomal formula by three folds indicating sustained release pattern. The relative bioavailability is also increased by 2.6 fold. The investigation proposed the rationality of cubosome to figure an effective controlled release tablets to improve its bioavailability and expand its activity.     

In vitro and in vivo evaluation of hydrophilic and hydrophobic polymers-based nicorandil-loaded peroral tablet compared with its once-daily commercial sustained-release tablet

Context: Hydrophilic and hydrophobic polymer-based nicorandil (10 mg)-loaded peroral tablets were prepared using the wet granulation technique. The influence of varying amounts of hydroxypropyl methylcellulose (HPMC) (30–50 mg), ethylcellulose (2–4 mg), microcrystalline cellulose (5–20 mg) and Aerosil^® (5–12 mg) in conjunction with the constant amounts (3 mg) of glidant and lubricant (magnesium stearate and talc) on the in vitro performances of the tablets (hardness, friability, weight variation, thickness uniformity, drug content, and drug release behavior) were investigated. Objective: The objectives of this study were (i) to select a nicorandil-loaded peroral tablet that matched the in vitro dissolution profile of once-daily commercial sustained-release tablet, and (ii) to compare the in vivo sustaining/controlling efficacy of the selected peroral tablet with that of its commercial counterparts. Results and Discussion: Because the nicorandil (10 mg)-loaded tablet prepared based on F-IX composition (50 mg HPMC, 4 mg ethylcellulose, 10 mg MCC and 3 mg glidant and lubricant) showed a release profile comparable to that of the Nikoran^® OD SR tablet release profile, the tablet with this composition was considered to be the optimized/selected formulation and, therefore, was subjected to stability study and in vivo study in rabbits. Despite of the higher C_max and AUC values obtained with the optimized tablet, there was no sign of difference between the optimized- and Nikoran^® OD SR- tablets following a single-dose crossover oral administration into rabbit. Conclusion: The optimized tablet could be used as an alternative to the commercial once-daily tablet.     

Buccal tablets containing cysteine and chlorhexidine for the reduction of acetaldehyde levels in the oral cavity

There is growing evidence that a large proportion of upper digestive tract tumors are ascribable to heavy alcohol drinking and tobacco consumption. The cancer-promoting action of ethanol is mediated by acetaldehyde, its first metabolite, also derived from the bacterial oxidation of alcohol by the oral microflora, classified by the International Agency for the Research on Cancer as a carcinogen. Acetaldehyde is also one of the major components of tobacco smoke. These findings suggest two different strategies to decrease the risk of alcohol-related oral cancers: the reduction of the levels of alcohol-derived acetaldehyde in saliva and the reduction of oral bacterial flora. Therefore, the aim of our study was to develop and characterize some buccal tablet formulations containing both 20?mg l-cysteine hydrochloride (able to chemically neutralize acetaldehyde) and 10?mg chlorhexidine diacetate (well-known antiseptic compound active against a large spectrum of oral microbes). One of these formulations, chosen on the basis of its favourable delivery kinetics of the active principles, was demonstrated to be able to reduce acetaldehyde concentration in an in vitro system and to lower its salivary levels in volunteers after ethanol contact. Our findings support the hypothesis that the application of buccal devices containing cysteine and chlorhexidine could reduce salivary acetaldehyde levels and thus the incidence of upper gastrointestinal cancer in drinkers and smokers.     

Development of dorzolamide hydrochloride in situ gel nanoemulsion for ocular delivery

Background: Several in situ gel-forming systems have been developed to prolong the precorneal residence time of a drug and to improve ocular bioavailability. Poloxamer 407 with its thermoreversible gelation and surface active properties was utilized to formulate a novel dorzolamide hydrochloride in situ gel nanoemulsion (NE) delivery system for ocular use. Objective: Improvement of both ocular bioavailability and duration of action for dorzolamide hydrochloride was the aim of this study. Methods: Physicochemical properties, in vitro drug release studies and biological evaluation of the prepared NEs were investigated. Results: The optimum formulation of in situ gel NE consisted of Triacetin (7.80%), Poloxamer 407 (13.65%), Poloxamer 188 (3.41%), Miranol C2M (4.55%), and water (70.59%). Biological evaluation of the designed dorzolamide formulation on normotensive albino rabbits indicated that this formulation had better biological performance, faster onset of action, and prolonged effect relative to either drug solution or the market product. The formula showed a superior pharmacodynamic activity compared to the in situ gel dorzolamide eye drops. This indicated the effectiveness of the in situ gel properties of poloxamer 407, besides formulating the drug in an NE form for improving the therapeutic efficacy of the drug. Conclusion: These results demonstrate the superiority of in situ gel NE to conventional ocular eye drops and in situ gels to enhance ocular drug bioavailability.     

Development of sustained release gastro-retentive tablet formulation of nicardipine hydrochloride using quality by design (QbD) approach

The objective of the present study was to develop a sustained release gastro-retentive (SRGR) tablet formulation of nicardipine hydrochloride (HCl) for once-a-day dosing using the quality by design (QbD) approach. The quality target product profile of nicardipine HCl SRGR tablet formulation was defined, and critical quality attributes (CQAs) were identified. Potential risk factors were identified using a fish bone diagram and failure mode effect analysis (FMEA) tool and screened by the Plackett–Burman design, and finally nicardipine HCl SRGR tablet formulation was optimized using the Box–Behnken design. The tablets were prepared by a direct compression technique using polymers such as hydroxypropylmethylcellulose (HPMC K15M), glyceryl behenate, alone or in combinations and other standard excipients. Sodium bicarbonate was incorporated as a gas-generating agent. The effects of polymers and sodium bicarbonate on the drug release profile and floating properties were investigated as these parameters are likely to affect the desired once-a-day dosing regimen and finally the therapeutic efficacy of SRGR drug delivery systems. It was observed that formulation variables X₁: Glyceryl behenate (mg/tab) and X₂: HPMC K15M (mg/tab) strikingly influenced the drug release (%) (Y₁), whereas floating lag time (min) (Y₂) was significantly impacted by the formulation variable X₃: Sodium bicarbonate (mg/tab). A design space plot within which the CQAs remained unchanged was established at a lab scale. In conclusion, this study demonstrated the suitability of a glyceryl behenate-HPMC K15M polymer combination along with sodium bicarbonate to achieve SRGR tablet formulation for once-a-day dosing of nicardipine HCl using the systematic QbD approach.     

An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet

A polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graceum L (family Fabaceae) was investigated for use in matrix formulations containing propranolol hydrochloride. Methocel^® hypomellose K4M was used as a standard controlled release polymer for comparison purposes. In this study the effect of lactose on the release behaviour of propranolol hydrochloride from matrices formulated to contain the fenugreek mucilage also was investigated. An increase in concentration of the mucilage in matrices resulted in a reduction in the release rate of propranolol hydrochloride comparable to that observed with hypomellose matrices. The rate of release of propranolol hydrochloride from fenugreek mucilage matrices was mainly controlled by the drug:mucilage ratio. However, the mechanism of release from matrices containing drug:mucilage ratios of 1:1, 1:1.25, 1:1.5, and 1:2 remained the same. The kinetics of release, utilising the release exponent n, showed that the values of n were between 0.46-0.57 indicating that the release from fenugreek mucilage matrices was predominantly by diffusion. The presence of lactose in matrices containing mucilage increased the release rate of propranolol hydrochloride. This is due to a reduction in tortuoisity and increased pore size of channels caused by lactose through which propranolol diffuses and therefore diffusion of water into the tablet is facilitated.     

Preparation,characterization and in vitro evaluation of microemulsion of raloxifene hydrochloride

Raloxifene hydrochloride (RLX) is a selective estrogen receptor modulator which is orally used for treatment of osteoporosis and prevention of breast cancer. The drug has low aqueous solubility and bioavailability. The aim of the present study is to formulate and characterize oil-in-water microemulsion systems for oral delivery of RLX. To enhance the drug aqueous solubility, microemulsion based on sesame oil was prepared. Sesame oil and Tween 80 were selected as the drug solvent oil and surfactant, respectively. In the first and second formulations, Edible glycerin and Span 80 were applied as co-surfactant, respectively. Pseudo-ternary phase diagrams showed that the best surfactant/co-surfactant ratios in the first and second formulations were 4:1 and 9:1, respectively. The particle size of all free drug-loaded and drug loaded samples were in the range of 31.25?±?0.3?nm and 60.9?±?0.1?nm, respectively. Electrical conductivity coefficient and refractive index of all microemulsion samples confirmed the formation of oil-in-water type of microemulsion. In vitro drug release profile showed that after 24?hours, 46% and 63% of the drug released through the first formulation in 0.1% (w/v) Tween 80 in distilled water as a release medium and phosphate buffer solution (PBS) at pH?=?5.5, respectively. These values were changed to 57% and 98% for the second formulation. Results confirmed that the proposed microemulsion system containing RLX could improve and control the drug release profile in comparison to conventional dosage form.     

Design and evaluation of soluble ocular drug insert for controlled release of ciprofloxacin hydrochloride

Purpose: Soluble ocular inserts of ciprofloxacin hydrochloride were prepared with the aim of achieving once a day administration. Design: Drug reservoir was prepared using natural hydrophilic polymer viz. gelatin while rate-controlling membrane was prepared using hydrophobic ethyl cellulose. Ocular inserts were evaluated for their physicochemical parameters like thickness, weight uniformity, drug content, percent moisture loss, and percent moisture absorption. The in vitro drug release studies were carried out using Bi-chambered donar receiver compartment model. Since targeted prolong release was observed in formulation CF2 and CF5, these formulations were further subjected to in vivo drug release study using rabbits as an animal model. In vitro drug release kinetic data was treated according to Zero, First, and Higuchi kinetics to access the mechanism of drug release. Results: Correlation between in vitro and in vivo drug release was found to be strong revealing the efficacy of the formulation. Conclusion: Formulation CF5 has achieved target of present study such as increase residence time, prolong drug release, reduction in frequency of administration, and, thus may improve the patient compliance.     

Design and optimization of gastric floating sustained-release mini-tablets of alfuzosin hydrochloride based on a factorial design: in vitro/in vivo evaluation

Abstract

The purpose of this research was to develop multiple-unit gastric floating mini-tablets and to evaluate the possibility of using these mini-tablets as a delivery system to improve the drug absorption for drugs with a narrow absorption window. Mini-tablets were prepared using hydroxypropyl methylcellulose (HPMC K100M) and carbopol 971P as release retarding agents and sodium bicarbonate (NaHCO₃) as gas-forming agent. The properties of the prepared mini-tablets in terms of floating characteristic parameters and in vitro release were evaluated. Furthermore, in vivo gastric retention study in rats and in vivo pharmacokinetic study in rabbits of the optimized formulation were performed. The optimized mini-tablets containing 45% HPMC K100M, 15% stearyl alcohol, 13% carbopol 971P, and 12% NaHCO₃ were found to float immediately within 1?min and duration more than 9?h. The in vivo gastric retention study results indicated that the mini-tablets could retain in the stomach for more than 6.67?h. Furthermore, the AUC_0?t of the floating mini-tablets (6849.83?±?753.80?h ng·mL^?1) was significantly higher than that of marketed sustained-release tablets XATRAL®XL (4970.16?±?924.60?h ng·mL^?1). All these results illustrated that the gastric floating mini-tablets might be a promising drug delivery system for drugs with a narrow absorption window.     

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.