Marketed Tablets Research Articles

Spectroscopic characterization and pharmacokinetic evaluation of amorphous solid dispersions of glibenclamide for bioavailability enhancement in Wistar rats.

Oral bioavailability of glibenclamide (Glb) was appreciably improved by the formation of an amorphous solid dispersion with Poloxamer-188 (P-188). Poloxamer-188 substantially enhanced the solubility and thereby the dissolution rate of the biopharmaceutics classification system (BCS) class II drug Glb and simultaneously exhibited a better stabilizing effect of the amorphous solid dispersion prepared by the solvent evaporation method. The physical state of the dispersed Glb in the polymeric matrix was characterized by differential scanning calorimetry, X-ray diffraction, scanning electron microscope and Fourier transform infrared studies. In vitro drug release in buffer (pH 7.2) revealed that the amorphous solid dispersion at a Glb-P-188 ratio of 1:6 (SDE4) improved the dissolution of Glb by 90% within 3h. A pharmacokinetic study of the solid dispersion formulation SDE4 in Wistar rats showed that the oral bioavailability of the drug was greatly increased as compared with the market tablet formulation, Daonil®. The formulation SDE4 resulted in an AUC0-24h ~2-fold higher. The SDE4 formulation was found to be stable during the study period of 6 months.

Desitometric Development and Validation for Simultaneous Determination of Antiretroviral Drugs Lamivudine, Zidovudine and Nevirapine in Fixed-Dose Combination Tablets

A cutting-edge high-performance thin layer chromatography (HPTLC) approach designed for simultaneous measurement of tablets containing drugs like lamivudine, nevirapine, and zidovudine. Chromatograms were performed employing chloroform and methanol (8:2 v/v) on pre-coated silica gel aluminum thin-layer chromatography (TLC) plates. The data was quantified using the optical density absorbance mode at 271 nm. The Rf values for lamivudine, zidovudine, and nevirapine were 0.140, 0.523, and 0.678, respectively. Linearity was found for lamivudine, zidovudine and nevirapine at concentrations of 150 to 900 ng band-1, 300 to 1800 and 200 to 1200 ng band-1, respectively. Lamivudine had a lower limit of detection (LLoD) of 27.36 ng band-1 and a lower limit of quantitation (LLoQ) of 82.91 ng band-1, whereas zidovudine had LoQs of 64.13 ng band-1 and 194.34 ng band-1. For nevirapine, the values were 35.52 and 107.64 ng band-1, respectively. Lamivudine had a lower LoD of 27.36 ng band-1 and a lower LoQ of 82.91 ng band-1, whereas zidovudine had LoQs of 64.13 and 194.34 ng band-1. For nevirapine, the values were 35.52 and 107.64 ng band-1, respectively. The recovery, specificity, and accuracy of this device have been demonstrated. This new formulation evaluated market tablet formulations of the above drugs (Duovir, Cipla Ltd.). The developed method demonstrated the ability to simultaneously identify these drugs from quantitative data without interference.

DESIGN, DEVELOPMENT, AND CHARACTERIZATION OF LORATADINE SUSTAINED RELEASED BUCCAL FILM: IN VITRO AND IN VIVO STUDY IN BEAGLE DOGS

Objective: The aim of this work was to develop and evaluate bucco-adhesive films of Loratadine (LTD) for sustained release use. Methods: Design of twelve different sustained released buccal film formulas using Carbopol, pectin, sodium alginate, glycerol, carboxymethyl cellulose (CMC), hydroxypropyl cellulose (HPC), Gelatin, Hydroxyethyl cellulose (HEC), and Hydroxypropyl methylcellulose (HPMC) as mucoadhesive polymers. Films were evaluated for physicochemical properties, thickness, swelling, moisture content, drug content, in vitro dissolution. The pharmacokinetic parameters of optimal formula were evaluated in beagle dogs. Results: The selected film formula (F6) showed accepted content and muco-adhesion properties. The in vitro release study showed prolonged release of drug from films over 10 h in optimal formulation. The bioavailability studies performed using beagle dogs model showed that there was 113.45% increase in the AUC0-24 of selected film compared with oral market tablets. Conclusion: Bucco-adhesive films is a promising dosage form for improving the bioavailability of loratadine.

Development of Transdermal Oleogel Containing Olmesartan Medoxomil: Statistical Optimization and Pharmacological Evaluation.

Olmesartan medoxomil (OLM) is a first-line antihypertensive drug with low oral bioavailability (28.6%). This study aimed to develop oleogel formulations to decrease OLM side effects and boost its therapeutic efficacy and bioavailability. OLM oleogel formulations were composed of Tween 20, Aerosil 200, and lavender oil. A central composite response surface design chose the optimized formulation, containing Oil/Surfactant (SAA) ratio of 1:1 and Aerosil % of 10.55%, after showing the lowest firmness and compressibility, and the highest viscosity, adhesiveness, and bioadhesive properties (Fmax and Wad). The optimized oleogel increased OLM release by 4.21 and 4.97 folds than the drug suspension and gel, respectively. The optimized oleogel formulation increased OLM permeation by 5.62 and 7.23 folds than the drug suspension and gel, respectively. The pharmacodynamic study revealed the superiority of the optimized formulation in maintaining normal blood pressure and heart rate for 24 h. The biochemical analysis revealed that the optimized oleogel achieved the best serum electrolyte balance profile, preventing OLM-induced tachycardia. The pharmacokinetic study showed that the optimized oleogel increased OLM's bioavailability by more than 4.5- and 2.5-folds compared to the standard gel and the oral market tablet, respectively. These results confirmed the success of oleogel formulations in the transdermal delivery of OLM.

Different types of pharmaceutical tablets used for treatment of diseases

In modern age of revolution and development in drug delivery for better clinical effects conventional dosages form have still a strong grip and most popular in all kinds of medicinal preparation intended for oral use. To satisfy the need of growing market tablets dosages form have incorporated modernization in producing and some advanced tablet types. Modified release tablet formulations including, layered tablets such as In +--lay tablet, Bi-layered tablet, Medicated chewing gum, Tablet tarts, Pastilles, Lollipop, Tablet inserts, Clinicaps, Caplets, Child ecstasy tablet and Tablet in tablet are new entries in pharmaceutical market. This review highlights the current advancements and patents in tablet technology. Recent advances in novel drug delivery system (NDDS) aims to enhance safety and efficacy of drug molecule by formulating a convenient dosage form for ease of administration and to achieve better patient compliance. In the recent trend one such approach the development of rapid disintegrating tablets formulation is emerging and gaining popularity because it is easy to administer and leads to better patient compliance. These dosage forms are placed in the mouth, allowed to disperse or dissolve in the saliva. They release the drug as soon as they come in contact with the saliva, thus obviating the need for water during administration. The aim of this article is to review the progress of the evolving technologies and super disintegrating agents in the formulation, manufacturing and evaluation of these tablets. This article also discusses the new evaluation methodologies for these rapid disintegrating tablets. Various modifications in the conventional evaluation and use of specialized instruments are found to be essential in the testing of these dosage forms. In the present review the formulation techniques and different technologies are discussed.

Assessment of MDMA tablet and capsule dosages from seizures in Queensland, Australia

3,4-Methylenedioxymethamphetamine (MDMA) is prominent in the illicit drug market and usually presents as tablets, capsules, or crystal. Drug purity determinations are typically performed in the Forensic Chemistry, Queensland Health Forensic and Scientific Services (QHFSS) laboratory on homogenised samples, yielding an average MDMA concentration which can be used to calculate average MDMA dosages (mg) per unit (i.e., tablet or capsule). Little published research exists however regarding individual dosage variability and drug content of capsules and tablets in the Australian illicit drug market. This study assessed selected tablet and capsule submissions as a part of routine casework over an 18-month period primarily to examine MDMA dosage variations between tablets or capsules within the same exhibit. Additionally, dosage variations from different seizures of the same logo or appearance were investigated where possible. Generally, tablet exhibits were found to have consistent dosages however, there were several instances where large variations were noted. These dosage variations were often attributable to inconsistent tablet whole weights, compounded by differences in MDMA concentration within tablets. MDMA dosage differences in capsule presentations were generally due to differences in capsule contents weight with some instances of individual capsules recording double the MDMA dosage of other capsules in the same seizure. To complement this study, results from all available MDMA detections from 2017 to 2020 in the QHFSS laboratory were examined. Average MDMA concentrations within tablets, capsules and crystal presentations increased during that time. Correspondingly, average MDMA dosages increased within capsule and tablet presentations, noting there was still a substantial range of MDMA dosages observed within capsule and tablet presentations. Finally, the presence of adulterants (psychoactive or non-psychoactive) in combination with MDMA was reported in a small proportion of cases, and more frequently in tablets than capsules. This study has provided a comprehensive survey and highlights the potential dosage variability that may be encountered in MDMA presentations in Queensland.

A novel oral medicated jelly for enhancement of etilefrine hydrochloride bioavailability: In vitro characterization and pharmacokinetic evaluation in healthy human volunteers

Etilefrine hydrochloride (ET) is a water-soluble drug that is used to treat hypotension, but it has a bitter taste and low bioavailability due to undergoing the first-pass effect. Thus, this study aimed to develop and evaluate oral medicated jelly (OMJ) containing ET that could offer an easily taken palatable dosage form with higher bioavailability. OMJ is a novel palatable drug delivery system that can easily be taken by pediatric and geriatric patients, as well as those with dysphagia. Moreover, OMJs offer rapid disintegration in saliva and rapid drug absorption through the buccal mucosa, avoiding the first-pass effect and increasing the drug bioavailability. Natural polymers such as pectin, guar gum, xanthan gum, tragacanth gum, and sodium alginate were used as jellifying agents, with the addition of calcium chloride as a crosslinking agent, to prepare OMJs using the heat and congealing method. The prepared OMJs were investigated by testing their viscosity, in vitro release, and texture analysis of firmness, consistency, stickiness, cohesiveness, springiness, gumminess, and chewiness using a texture analyzer. A full factorial design (21 × 51) was utilized to select the optimized OMJ. The optimized OMJ (J2), containing 4 % pectin, had a 7563 ± 55 cps viscosity, 8.32 ± 0.21 N firmness, 5.72 ± 0.18 µJ consistency, 1.30 ± 0.04 mJ stickiness, and 96.02 ± 3.74 % ET dissolved after 10 min. ET release was significantly increased (greater than4-fold) from the optimized OMJ compared with the market tablet. Moreover, the obtained results clarified the stability and the acceptable palatability of the optimized OMJ. The clinical investigation on healthy human volunteers revealed that the optimized OMJ (J2) had significantly higher Cmax (1.7 folds) when compared with the market tablet with a relative bioavailability of 154.55 %. Therefore, OMJs can be considered as promising, palatable, and easily swallowed dosage form that could enhance the bioavailability of drugs undergoing the first-pass effect.

Synthesized nano particles of glimepiride via spray freezing into cryogenic liquid: characterization, antidiabetic activity, and bioavailability

The aim of this work was to formulate glimepiride (class II drug) which is characterized by low solubility and high permeability as nanostructured particles using a cryogenic technique with an aid of water-soluble polymer to improve its aqueous solubility and hence its bioavailability. 27 formula of glimepiride nano size particles were prepared by a spray freezing into cryogenic liquid (SCFL) using poly vinyl pyrrolidone K-30 (PVP K-30); that three drug polymer ratio (1:1, 1:2, and 1:3), with three different volumes of feeding solution (50, 100, 150 mL), at three flow rates (10, 20, and 30 mL/min). The prepared formulations were evaluated for production yield, particle size, zeta potential, drug content, release rate, in vivo hypoglycemic activity, and bioavailability. All prepared formulations showed high production yield and drug content ranged between 91.1 ± 3.4% and 94.3 ± 1.8% and 95.1 ± 2.8% and 97.1 ± 2.5%, respectively. The mean particles size was ranged between 280 ± 62 nm and 520 ± 30 nm. The results of in vitro release study revealed significant enhancement in the solubility of prepared formulations compared with the pure drug. It was found that optimal formula showed a significant reduction in blood glucose levels in diabetic rats, and 1.79-fold enhancements in oral bioavailability compared with market tablets. Nanoparticle prepared by SCFL method is an encouraging formula for improving the solubility and the bioavailability of glimepiride.

A SIMPLE SENSITIVE AND RAPID GAS CHROMATOGRAPHY METHOD FOR DETECTION AND QUANTIZATION OF METFORMIN IN METFORMIN TABLET FORMULATION, BY DIRECT INJECTION, USING MASS DETECTOR

Metformin (1, 1- dimethyl biguanide) represents the “gold standard” for the treatment of diabetes mellitus type 2. Despite its important role in reducing mortality and morbidity in the diabetic population, metformin is associated with an increased risk of stroke. A simple, novel, specific, and sensitive gas chromatography-mass spectrometry method (GC-MS) for the determination of metformin was developed. Several parameters such as reaction time and temperature were optimized. There was no interfering peak from the blank at the retention time of metformin. Linearity was demonstrated over the concentration range of 4.024–24.144ppm with a coefficient of determination (R2) above 0.9999. Accuracy and precision were within acceptable limits. The method was fully validated using parameters such as specificity, linearity, limits of detection and quantification, precision, accuracy, recovery, range, robustness, and ruggedness. The developed method was successfully applied for the identification and quantification of metformin in the market tablet formulation.

Formulation of Lipid-Based Tableted Spray-Congealed Microparticles for Sustained Release of Vildagliptin: In Vitro and In Vivo Studies.

Spray-congealing (SPC) technology was utilized to prepare lipid-based microparticles (MP) capable of sustaining the release of Vildagliptin (VG) for use as a once-daily treatment for type 2 diabetes mellitus. VG microparticles were prepared using Compritol® and Gelucire®50/13 as lipid carriers in the presence of various amounts of Carbomer 934 NF. The lipid carriers were heated to 10 °C above their melting points, and VG was dispersed in the lipid melt and sprayed through the heated two-fluid nozzle of the spray congealer to prepare the VG-loaded MP (VGMP). The microparticles produced were then compressed into tablets and characterized for their morphological and physicochemical characteristics, content analysis, in vitro dissolution, and in vivo bioavailability studies in mixed-breed dogs. The VGMP were spherical with a yield of 76% of the total amount. VG was found to be in its semicrystalline form, with a drug content of 11.11% per tablet and a percentage drug recovery reaching 98.8%. The in vitro dissolution studies showed that VG was released from the tableted particles in a sustained-release fashion for up to 24 h compared with the immediate-release marketed tablets from which VG was completely released within 30 min. The in vivo pharmacokinetics studies reported a Cmax, Tmax, T1/2, and MRT of 118 ng/mL, 3.4 h, 5.27 h, and 9.8 h, respectively, for the SPC formulations, showing a significant difference (p < 0.05)) from the pk parameters of the immediate-release marketed drug (147 ng/mL, 1 h, 2.16 h, and 2.8 h, respectively). The area under the peak (AUC) of both the reference and tested formulations was comparable to indicate similar bioavailabilities. The in vitro–in vivo correlation (IVIVC) studies using multiple level C correlations showed a linear correlation between in vivo pharmacokinetics and dissolution parameters. In conclusion, SPC was successfully utilized to prepare a once-daily sustained-release VG oral drug delivery system.

Formulation and Development of Oral Fast-Dissolving Films Loaded with Nanosuspension to Augment Paroxetine Bioavailability: In Vitro Characterization, Ex Vivo Permeation, and Pharmacokinetic Evaluation in Healthy Human Volunteers.

Paroxetine (PX) is the most potent serotonin reuptake inhibitor utilized in depression and anxiety treatment. It has drawbacks, such as having a very bitter taste, low water solubility, and undergoing extensive first pass metabolism, leading to poor oral bioavailability (<50%). This work aimed to develop and optimize palatable oral fast-dissolving films (OFDFs) loaded with a paroxetine nanosuspension. A PX nanosuspension was prepared to increase the PX solubility and permeability via the buccal mucosa. The OFDFs could increase PX bioavailability due to their rapid dissolution in saliva, without needing water, and the rapid absorption of the loaded drug through the buccal mucosa, thus decreasing the PX metabolism in the liver. OFDFs also offer better convenience to patients with mental illness, as well as pediatric, elderly, and developmentally disabled patients. The PX nanosuspension was characterized by particle size, poly dispersity index, and zeta potential. Twelve OFDFs were formulated using a solvent casting technique. A 22 × 31 full factorial design was applied to choose the optimized OFDF, utilizing Design-Expert® software (Stat-Ease Inc., Minneapolis, MN, USA). The optimized OFDF (F1) had a 3.89 ± 0.19 Mpa tensile strength, 53.08 ± 1.28% elongation%, 8.12 ± 0.13 MPa Young’s modulus, 17.09 ± 1.30 s disintegration time, and 96.02 ± 3.46% PX dissolved after 10 min. This optimized OFDF was subjected to in vitro dissolution, ex vivo permeation, stability, and palatability studies. The permeation study, using chicken buccal pouch, revealed increased drug permeation from the optimized OFDF; with a more than three-fold increase in permeation over the pure drug. The relative bioavailability of the optimized OFDF in comparison with the market tablet was estimated clinically in healthy human volunteers and was found to be 178.43%. These findings confirmed the success of the OFDFs loaded with PX nanosuspension for increasing PX bioavailability.

Formulation, characterization, optimization, and in-vivo performance of febuxostat self-nano-emulsifying system loaded sublingual films

Febuxostat (FXS) is a potent antigout drug with poor water solubility and relative high first-pass effect leading to moderate oral bioavailability (<49%). This study aimed to increase FXS solubility and bioavailability by optimizing sublingual fast-dissolving films (SFs) containing a selected FXS self-nano-emulsifying system (s-SNES) previously prepared by our team. The s-SNES was loaded into SFs by solvent casting technique. A full factorial design (32) was applied to study the effects of polymer and plasticizer types on mechanical characteristics and the dissolution profile of FXS from the SFs. Numerical optimization was performed to select the SF having highest desirability according to predetermined characteristics. The optimized SF (O-SF) contained 1 g of s-SNES, polyvinylpyrrolidone K30 (6%w/v), polyethylene glycol 300 (20%w/w of polymer wt.), and Avicel PH101 (0.5%w/v). O-SF showed good permeation of FXS through sheep sublingual tissue. Storage of O-SF for three months showed no significant change in the FXS dissolution profile. In-vivo performance of O-SF in rabbits was compared to that of oral marketed tablets (Staturic® 80 mg). A cross-over design was applied and pharmacokinetic parameters were calculated after ensuring absence of sequence effect. Statistical analysis revealed better performance for O-SF with significantly higher C max, AUC0–24, AUC0–∞, apparent t 1/2 together with lower t max, and apparent kel than marketed tablets. Relative bioavailability of O-SF compared to the marketed tablet was found to be 240.6%. This confirms the achievement of the study aims of improving dissolution rate and bioavailability of FXS using a patient-wise convenient formula.

Višečestične formulacije lekova za oralnu primenu kao strategija za precizno doziranje kod pedijatrijskih pacijenata - studija slučaja propranolola

The development of solid dosage forms that are both convenient for administration and allow precise drug dosing for pediatric patients is one of the great challenges in contemporary pharmaceutical technology. The presented study has utilized propranolol hydrochloride, as one of the most frequently prescribed drugs that require manipulation of the conventional dosage forms to be administered to children. Multiparticulate oral formulations, powderand granulefilled capsules, as well as mini tablets, were prepared and characterized in terms of their mass and content uniformity and compared to conventional marketed tablets split into halves and quarters. The obtained results have demonstrated the superiority of the multiparticulate formulations, in terms of their average mass and drug content uniformity. It has also been demonstrated that, due to improved flowability, granule-filled capsules are more conveniently compounded and provide higher content uniformity compared to powder-filled capsules. The presented compounding method could be easily employed in community pharmacy settings. Mini tablets with high and uniform content of propranolol hydrochloride have been successfully prepared, thereby presenting a viable strategy for efficient drug dose adjustment.

Efficient design to fabricate smart Lumefantrine nanocrystals using DENA® particle engineering technology: Characterisation, in vitro and in vivo antimalarial evaluation and assessment of acute and sub-acute toxicity

Nanocrystalization technologies have a great potential to substantially increase solubility as well as alleviate the erratic bioavailability behaviour of a range of poorly water soluble drugs. The aim of the current study was to fabricate smart nanocrystals of lumefantrine (LF) using wet milling technology (DENA DM-100) with the subsequent in vitro, in vivo evaluation and toxicity screening. This technology successfully produced nanocrystals with an average particle size (214.1 ± 0.2 nm) and PDI (0.201 ± 0.06) in a period of less than 1 h. DSC and PXRD were used to confirm crystallinity of the processed LF. The dissolution rate and saturation solubility of the processed LF was significantly (P < 0.05) increased compared to the raw and marketed tablets. The IC50 value of LF nanocrystals was significantly (P < 0.05) lower than the IC50 value of the raw drug and marketed tablets. In addition, LF nanocrystals at the same dose (30 mg/kg), showed significantly (P < 0.05) the highest reduction in the percentage of parasitemia compared to its other counterparts against P. vivax. The LD50 value of LF nanocrystals in the acute toxicity was between 1000 and 1500 mg/kg and was devoid of any observable sub-acute toxicity. The histopathological investigations and impact of LF nanocrystals on different internal organs of the chosen animal model were found comparable to the saline treated animal group. The results of current study suggested that wet milling can be effectively used to fabricate nanocrystals of LF both in acidic and aqueous media with enhanced antimalarial activities and a similar safety profile.

Comparative Physicochemical Evaluation of Selective Brands of Diclofenac Potassium Tablets Available in Pakistan

The purpose of present effort was to conduct physiochemical evaluation of miscellaneous commercially available diclofenac potassium 75 mg tablets in the local market of Sindh, Pakistan. Further comparison was made among their different parameters. In study seven brands tagged as RB1 to RB7 were evaluated for diameter, thickness, disintegration time, and assay content and dissolution profile. Obtained results of all brands conformed to the official standard specification for disintegration test, Assay Content. The attained release rate profile during dissolution study revealed that all brands achieved more than 80% in sixty minutes. The spectrophotometric analysis for assay content of all brands was within 90%-110% which in good agreement with specified in the Unites States Pharmacopoeia. In the current study all the assessed products could be regarded as being chemically similar, while no product is found as a false product, these all brands can be used alternatively. The used spectrophotometric evaluation is very simple, reasonable, and easy to adopt for analysis and could be used in routine analysis of diclofenac potassium tablets, particularly in the unavailability of advanced equipment’s just like HPLC, LCMS &amp; GC etc. which is not easily available and accusable in many institutions.

Quantification of albendazole in tablets of combined composition

The Aim: Treatment of helminthiases of the digestive system remains an actual task of the medicine and pharmacy worldwide. So, to meet the needs of the Ukrainian pharmaceutical market tablets based on albendazole and praziquantel were proposed. In order to establish the further production of the drug, studies were conducted on the development and validation of a method for the quantitative determination of one of the active substances – albendazole, in the presence of the second active substance praziquantel. Materials and Methods: The object of the study was samples of tablets under the conditional name “AP-helmin”. Albendazole was extracted from tablets with ethyl alcohol when heated, 0.1 M sodium hydroxide solution was added and the obtained sample was evaluated spectrophotometrically in the ultraviolet light (308 nm). The method was conducted meeting the requirements of State Pharmacopoeia of Ukraine, harmonized with the relevant European Pharmacopoeia techniques. Results: The samples comply with the Bouguer-Lambert-Behr law in the concentration range 1 × 10-3 - 1.2 × 10-2 mg/ml, the correlation coefficient is ≥ 0.9998. The studied method of quantitative determination of albendazole in the drug meets the criteria of acceptability for the range of determination ± 5.0 % by validation characteristics: specificity, linearity, precision, accuracy. The criterion of insignificance of the systematic error of the method is fulfilled – the systematic error of the method (0.24) is practically insignificant, that is, the method of analysis is characterized by sufficient correctness in the whole concentration range from 80 to 120 %. All the validation characteristics respond to the acceptance criteria. Conclusions: A method for the quantitative determination of albendazole in tablets “AP-helmin” by spectrophotometry in ultraviolet light (308 nm) was worked out. It was experimentally confirmed that the second active pharmaceutical ingredient (praziquantel) had no affect the accuracy of the results obtained.

Core in Cup Ethylmorphine Hydrochloride Tablet for Dual Fast and Sustained Pain Relief: Formulation, Characterization, and Pharmacokinetic Study.

Ethylmorphine hydrochloride (EtM) is a derivative of morphine used as analgesic to treat severe pain in case of cancer and bone injury. This study aimed to formulate and evaluate core in cup tablets containing 2 doses of EtM, the cup was formulated as lyophilized oro-dispersible tablet (ODT) for immediate release (IR), and the core was formulated as directly compressed tablet for sustained release (SR). Factorial design was adopted for the optimization of tablets prepared via lyophilized form and direct compression techniques: a 41.22 design was used for the former, while a 32 one was used for the latter. All prepared tablets showed acceptable physical properties which were in accordance with pharmacopeial standards. Two lyophilized ODTs (F9 and F10) formulae were selected as the cup for instant release. While one directly compressed tablet formula (S6) was selected based on the in vitro release profile to represent the sustained core, the outcome was 2 core in cup tablets, namely B1 and B2 which were evaluated for their in vivo absorption and showed a maximum plasma concentration (Cpmax) of 354.12 ± 17.55 ng/mL and 350.82 ± 12.15 ng/mL respectively attained after 3.0 h which were twofolds significantly higher in comparison to the market tablet with Cpmax of only 172.05 ± 12.53 ng/mL attained after 2.20 ± 0.24 h.

Formulation of lyophilized oily-core poly-Ɛ-caprolactone nanocapsules to improve oral bioavailability of Olmesartan Medoxomil

Objective: This study aims to detect the enhancement in the oral bioavailability of a poorly water-soluble antihypertensive drug Olmesartan Medoxomil (OM) due to the formulation of lyophilized oily-core nanocapsules.Significance: A comparative pharmacokinetic study in rats was conducted for oily-core polymeric nanocapsules (ONC) after formulation and lyophilization against market tablet products to show the significant improvement in oral absorption of OM.Materials and methods: OM loaded ONC were prepared using poly-Ɛ-caprolactone (0.5% w/v) as a polymer and an oily core of Labrafac PG® by applying a well-controlled nanoprecipitation technique in terms of injection rate (80 mL/h) and magnetic stirring rate (300 rpm). The prepared lyophilized ONC were in-vitro characterized after reconstitution and evaluated in-vivo for oral bioavailability after a single OM oral dose (20 mg/kg) of reconstituted lyophilized ONC dispersion was administered to rats.Results: The prepared lyophilized ONC containing 10% w/v mannitol showed an average particle size of 158 nm, polydispersity index of 0.37, negative zeta potential value equals 33.9 and entrapment efficiency of 90%. The dissolution profile for OM from lyophilized ONC powder filled into hard gelatin capsules (HGC) showed a 1.8-fold increase in dissolution rate as compared to the pure drug. In-vivo pharmacokinetic study in rats revealed a significant enhancement in the oral bioavailability of OM with 1.6-fold increase for AUC0-24 and a 1.9-fold increase for Cmax as compared to marketed product.Conclusion: It is concluded that the formulation of lyophilized ONC for OM can significantly enhance its oral bioavailability and consequently, its therapeutic efficacy and patient compliance.

Combined site-specific release retardant mini-matrix tablets (C-SSRRMT) for extended oral delivery of dexketoprofen trometamol: in vitro evaluation and single versus multiple doses pharmacokinetic study in human volunteers

Development of extended release oral formulations of dexketoprofen trometamol (DT), a rapidly eliminated drug with high solubility, poses a great challenge especially when a portion of the dose is to be absorbed from the colon. In this study, site-specific release-retardant mini-matrix tablets (SSRRMTs) were developed and functionally coated with pH-responsive materials to achieve a site-specific delivery of DT at the duodenojejunal (DSRRMT) and ileocecal (ISRRMT) regions. Stomach-specific coated mini-tablets (SSCMTs) were manufactured for immediate release of about 16% of the daily dose of DT in the stomach. The SSCMT, DSRRMT, and ISRRMT were combined into a solid dosage form (C-SSRRMT tablets or capsules) to achieve the required linear release profile for once daily administration of DT. The SSRRMT and C-SSRRMT formulations were evaluated for the physical properties, in vitro-disintegration and in vitro dissolution and proved to be consistent with the pharmacopeial specifications. The in vitro release profiles of both C-SSRRMT tablets and capsules showed a constant release rate of about 6 mg/h and were similar to that of the theoretical target linear release profile. The pharmacokinetic study using human volunteers showed the bioequivalence of a single oral dose of C-SSRRMT capsules compared to three-successive oral doses of the immediate release market tablets with less ups and downs in the drug levels. The C-SSRRMT capsules formulation, may therefore, constitute an advance in the extended oral delivery of DT without the lack of efficacy and the adverse events frequently encountered in multiple daily dosing of the immediate release tablets.

NOVEL ORAL DELIVERY OF IBUPROFEN SOLUTION IN HARD GELATIN CAPSULES

Objective: The primary objective of the project was to formulate and evaluate hard capsule containing the solution of ibuprofen. It also included enhancement of solubility of ibuprofen in hydrophilic solvents to obtain a unit dose capsule acceptable for human consumption.&#x0D; Methods: Solution of ibuprofen was developed by the salt formation of partial drug using potassium hydroxide in PEG 600 and water. The solution was encapsulated in hard capsules with band sealing. The final formulation was evaluated for uniformity of weight, disintegration, drug content and stability. The dissolution profile was compared with that of available marketed tablets and softgels.&#x0D; Results: The capsules were evaluated and found compliant as per specifications mentioned in general monograph of capsules in IP 2014. The uniformity of weight of the batch of capsules was found to be 734.8 mg (±0.58). The disintegration time of these capsules was observed to be 4.45 min. The drug content was found to be 100.03% and the product is stable over three months of test period under room temperature as well as accelerated conditions. The dissolution profile showed that softgels take longer time to release the drug whereas marketed tablets showed a dissolution profile comparable with that of formulated capsules.&#x0D; Conclusion: The developed capsule is a unit dose of liquid containing solubilized ibuprofen delivering the drug directly into the gastrointestinal tract (GIT). These are newer solid oral dosage forms with higher patient compliance and ease in manufacturing. They require lesser steps and manufacturing area when compared to the manufacturing of compressed tablets.