Drug-excipient Interaction Studies Research Articles

Quality by design-based development and in vitro evaluation of dual release tablet of etoricoxib and thiocolchicoside: A novel chronotherapeutic approach for arthritis pain management

The traditional drug delivery system is not much effective when treating chronopathological diseases like arthritis. Consequently, there is a gap in the market for a delivery system that can provide an explicit treatment following the chronopharmacology of this disorder. The present study is based on the objective to develop Eudragit coated dual release bilayer tablet designed by the quality by design (QbD) and based on the chronotherapeutic approach. The dual release tablet contained an immediate release layer of etoricoxib and a sustained release layer of thiocolchicoside. The quality target product profile (QTTP) of the formulation was established along with critical quality attributes (CQA). The optimization of the dual release layer was done using a three-level, three-factor Box-Behnken design. A total of thirteen formulations of etoricoxib (ET1-ET13) and thiocolchicoside (TH1-TH13) were developed based on the design composition of etoricoxib, sodium starch glycolate and sodium bicarbonate for the immediate release (IR) layer and thiocolchicoside, HPMC E5 LV and magnesium stearate for the sustained release (SR) layer respectively. The developed dual release layers were compressed to form a bilayer tablet. The bilayer tablets were further coated with pH-dependent polymer Eudragit S-100 to avoid drug release in upper GIT. The initial characterization and drug-excipient interaction studies were performed initially using infra-red (IR) spectroscopy and X-ray diffraction studies (XRD). Formulations showing good micrometric properties, disintegration and drug release were selected for final compression of bilayer tablets. Formulation ET13 showed the fastest drug release (88%) at 15minutes and quick disintegration time (21s). The sustained release thiocolchicoside tablet layer (TH1-TH13) had a hardness that varied from 4.01 to 4.45kg/cm2. Formulation TH12 had the highest hardness, whereas TH6 showed the lowest hardness. The sustained release layer showing 97.63% of drug release after 8hours was selected for the compression to bilayer tablet. The developed dual layer tablets were investigated for quality parameters like hardness, percentage friability, weight variation, disintegration and dissolution. A high level of patient compliance is ensured through the current design as the patient does not need to get out of bed at night to take the medication.

Development and In Vitro Evaluation of Nanoparticles of Silymarin Using Central Composite Design

Silymarin is a phytoconstituent derived from the plant Silybum marianum with poor oral absorption and bioavailability but possesses hepatoprotective activity, anticancer activity, cardioprotective, neuroprotective, stabilizing, anti-inflammatory, and antioxidant activity. Therefore, the current work aims to develop a nanoformulation of silymarin to increase bioavailability, reduce dosing frequency, minimize toxicity, and improve patient compliance. Silymarin nanoparticles were created via the ionic gelation technique, employing chitosan and TPP as the primary polymers. A central composite design was employed for formulation optimization. Chitosan and TPP were employed as independent variables, while particle size and encapsulation efficiency were considered as dependent variables. The prepared nanoparticles were evaluated through entrapment efficiency, in vitro drug release, and drug-excipient interaction studies. Thirteen experiments were conducted using the experimental runs created by the central composite design. The average particle size was between 149nm and 294nm. The encapsulation efficiency percentage was between 65.4% and 87.3%. The polydispersity index had a value of 0.437. The zeta potential of the optimized formulation was determined to be 38.1 mV. The compatibility studies between the drug and excipients were confirmed using Fourier Transform Infrared Spectroscopy and Differential Scanning Calorimetry. The successful encapsulation of silymarin within the polymer core was verified through scanning electron microscopy analysis. The silymarin-loaded nanoparticles were observed to have a significant drug release of 98,942.43% over 24 hours. The outcomes of the study of Silymarin nanoparticles showed a substantial increase in the dissolution rate, which can be ascribed to the changed solubility properties of the drug. This result is consistent with the stated aim of improving drug absorption. Keywords: Silymarin, nanoformulation, central composite design.

DEVELOPMENT AND CHARACTERIZATION OF SELF-HEALING TRANSDERMAL PATCH OF LIDOCAINE FOR THE MANAGEMENT OF PAIN

Pain management is a significant challenge due to the side effects associated with commonly prescribed medications like NSAIDs and opioids. Local anesthetics, such as lidocaine, offer an alternative with fewer side effects when formulated in topical patches. Transdermal delivery systems, including heated patches, enhance drug absorption and provide targeted pain relief. This research paper aims to develop and characterize a self-heating transdermal patch of lidocaine for pain management. The drug sample of lidocaine was characterized using UV-visible spectrophotometric analysis, melting point determination, and differential scanning calorimetry. The results confirmed the purity of the drug sample. Pre-formulation studies were conducted to determine the solubility and partition coefficient of lidocaine, as well as drug-excipient interaction studies. The formulation of the lidocaine transdermal patch included the selection of excipients such as solvents, adhesives, solubilizers, and permeation enhancers. The patch was developed in three trial batches, with the final batch prepared using a drug-in-adhesive type approach. The developed patch was evaluated for physical characteristics, solvent residual content, rolling ball test, shear strength, drug crystallization, drug content, and in-vitro permeation. The results of the evaluation showed that the developed lidocaine transdermal patch had the desired physical characteristics, uniform thickness, good folding endurance, and appropriate solvent residual content. It exhibited satisfactory rolling ball test and shear strength. Microscopic examination confirmed the absence of drug crystallization. The drug content of the patch was determined to be within the desired range, and the in-vitro permeation study demonstrated successful drug release through the dialysis membrane. In conclusion, the development and characterization of a self-heating transdermal patch of lidocaine for pain management provide a promising approach for effective and targeted pain relief. The patch formulation demonstrated suitable physical properties, drug content, and permeation characteristics, suggesting its potential as an alternative pain management solution. KEYWORDS: Lidocaine, transdermal patch, pain management, self-heating, drug delivery

Transferosomal gel for transdermal delivery of insulin: Formulation development and ex vivo permeation study

The study was to develop a transdermal formulation of insulin, determine its pharmaceutical characteristics, and finally test its efficacy. In the current study - Transfersomes were selected as the carrier system for insulin. The transfersomes were produced by the hand-shaking method using soy lecithin phospholipid and sodium deoxycholate as the objective of the surfactant. The prepared transfersomes were subjected to characterization with optical microscopy and scanning electron microscope to estimate the shape and size of transfersomes respectively. In addition, the physical and drug-excipient interaction studies were carried out and the transfersomes were also studied for the insulin entrapment efficiency.Results of the study showed the shape of the transfersomes was well defined and spherical. The mean size of transfersomes was estimated to be 130 ​nm The transfersomes were found to be stable over a period of four weeks. The insulin entrapment efficiency of the transfersomes was estimated to be 87.3%. The ex-vivo skin permeation study employing goat ear skin with the transfersomes hydrogel revealed that there was a slow and sustained release of insulin till 180 ​min. From the above study, it may be concluded that transfersomes are suitable carriers of insulin across biological membranes.

DEVELOPMENT AND IN VITRO EVALUATION OF PHYTOSOMES OF ELLAGIC ACID

Objectives: The main objective of the present work is to enhance the bioavailability of ellagic acid (EA) by increasing its dissolution there by allowing for the exploitation of its therapeutic effects. Methods: Phytosomes containing EA were prepared by anti-solvent precipitation method. The prepared phytosomes were evaluated for drug entrapment efficiency, in vitro drug release, and drug excipient interaction studies. Results: Formulation F2 containing EA and soya lecithin in the ratio (1:2) showed highest percentage of drug release as 85.40% in 60 min and 95.86% in 120 min. The drug entrapment efficiency values were satisfactory. There were no interactions between the drug and the excipients used in its preparation according to Fourier-transform infrared spectra of pure EA and EA phytosomes. Conclusion: Phytosomes of EA were successfully produced by anti-solvent precipitation method and the percentage drug entrapment efficiency was satisfactory in almost all formulations. Formulation F2 exhibited highest percent of drug release as 85.40% in 60 min and 95.86% in 120 min to possess optimum bioavailability.

Investigation of the Tableting Properties of Modified Dioscorea dumetorum Starch in Direct Compressed Diclofenac Tablet Formulations

Background: Modification of starch enhances their performance and improves properties such as compressibility, visco-stability, texture and dissolution. Objectives: The aim of the study was to investigate the direct compression properties of modified starch of Dioscorea dumetorum in diclofenac tablet formulations. Method: Isolated starch from Dioscorea dumetorum tubers was subject to two forms of modification and the modified products characterized with the native starch for their physicochemical and powder properties. The modified starches (5, 7.5 and 10%w/w) and microcrystalline cellulose (MCC) (10%w/w) were used in the formulation of batches of diclofenac potassium tablets via slugging and direct compression. Flowability of granules from their slugs and tablet parameters from their tablet were evaluated using standard procedures. Drug-excipient interaction studies was carried out using FTIR analysis. Results: The extracted starch was white, while the modified forms were off-white in colour. All the starches were smooth in texture and insoluble in water with swelling capacities ≤ 2.85, hydration capacities ≥ 1.22 and moisture contents ≤ 14.5%. Granules gave Carr’s indices, Hausner’s ratios and angles of repose values ranging from 10.71-18.03%, 1.12-1.22 and 20.16- 28.15°, respectively, indicating good flow. Tablet’s friability ranged from 0.01-0.04% while their hardness values was between 4.20-5.50 kp and disintegration times < 7.0 min. Dissolution profiles of the tablets showed over 70% diclofenac release within 45 min. FTIR studies showed no interaction between diclofenac and formulation excipients. Conclusion: Modified Dioscorea dumetorum starch possesses binding and disintegrating properties comparable with MCC, hence it can be used as an alternative to MCC in direct compression of tablets.

Design and Characterization of Buccal Films of Benzocaine for Mouth Ulcer

Mouth ulcer is very common in recent years, which occurs due to the damage of epithelial tissue and/or lamina propria that finally leads to tissue necrosis. Benzocaine has been used to treat the mouth ulcers due to its excellent local anaesthetic effect that relieves the pain associated with mouth ulcer. Hence an attempt was made to develop and characterize the buccal films of Benzocaine to treat mouth ulcers with an aim of prolonging the drug release and improving the patient convenience. The films were fabricated using the mucoadhesive polymer blend of chitosan and HPMC by solvent casting method and the physico-mechanical, in vitro drug release and ex vivo buccal mucosal permeation characteristics of the films were studied. All fabricated film formulations prepared were smooth and almost opaque, with good flexibility. The weight and thickness of all the formulations were found to be uniform. Drug content in the films ranged from 97–99%, indicating favorable drug loading and uniformity. The inclusion of HPMC, significantly reduced the bioadhesive strength and in vitro mucoadhesion time of chitosan films, although the degree of swelling increased. In vitro drug release and permeation studies in simulated saliva showed a prolonged release for a period of 6 h for all formulations. The formulation with Chitosan: HPMC ratio 1:1, 10% w/w polysorbate 80 and 10% w/w propylene glycol as plasticizers showed the best results which exhibited the cumulative percentage drug release of 87.9 % and the cumulative amount of drug permeation of 7.62mg/cm2 across goat buccal mucosa in 6 h. Drug-excipient interaction studies were carried out using DSC and FT-IR technique; films indicated no chemical interaction between drug and polymers used. Keywords: Benzocaine; mouth ulcer; mucoadhesion; buccal film

Development, Formulation and Evaluation of Sustain Release Dispersible Tablet of Ornidazole

This Present research with dispersible tablet can compromise the efficacy and safety of the treatment to children’s and geriatric patients with masking the bitter taste of drug and developing its dispersible tablet. The purpose of this research work was to develop Dispersible tablet of Ornidazole by masking the bitter taste. Tablet containing drug and excipients were prepared by direct compression method. Excipients in combinations were incorporated to achieve the aim. Effect of different combinations was studied to optimize the ideal formulation. Drug excipients interaction studies were carried out by FTIR spectral analysis. The tablets were evaluated for their hardness, wetting time, disintegrating time and dissolution parameters. It was concluded that the tablets having the combination of Dried Mucilage (obtained from dried seeds of ocimum bacilicum) and Sodium starch glycolate met all the evaluation parameters and thus selected as the optimized formulation. Optimized formulation was undergone for stability testing as a parameter to predict the shelf life as per ICH guidelines and proved for its adequate shelf life.

3 (2) Factorial Design Assisted Crushed Puffed Rice-HPMC-Chitosan based Hydrodynamically Balanced System of Metoprolol Succinate

Introduction: Hydrodynamically balanced system (HBS) possesses prolonged and continuous delivery of the drug to the gastrointestinal tract which improves the rate and extent of medications that have a narrow absorption window. The objective of this work was to develop a Hydrodynamically Balanced System (HBS) of Metoprolol Succinate (MS) as a model drug for sustained stomach specific delivery. Materials and Methods: Experimental batches were designed according to 3(2) Taguchi factorial design. A total of 9 batches were prepared for batch size 100 capsules each. Formulations were prepared by physically blending MS with polymers followed by encapsulation into hard gelatin capsule shell of size 0. Polymers used were Low Molecular Weight Chitosan (LMWCH), Crushed Puffed Rice (CPR), and Hydroxypropyl Methylcellulose K15 M (HPMC K15M). Two factors used were buoyancy time (Y1) and time taken for 60% drug release (T60%; Y2). Results: The drug excipient interaction studies were performed by the thermal analysis method which depicts that no drug excipient interaction occurs. In vitro buoyancy studies and drug release studies revealed the efficacy of HBS to remain gastro retentive for a prolonged period and concurrently sustained the release of MS in highly acidic medium. All formulations followed zero-order kinetics. Conclusion: Developed HBS of MS with hydrogel-forming polymers could be an ideal delivery system for sustained stomach specific delivery and would be useful for the cardiac patients where the prolonged therapeutic action is required.

Chewable Tablets of Acacia catechu Extract, an Alternative to Betel (Paan) for Mouth Ulcers: Formulation and In vitro Evaluation.

The objective of the current research work was to prepare chewable tablets having Acacia catechu extract useful for mouth ulcers using a 32 factorial design. Acacia catechu heartwood extract was prepared using a reported method with some modifications. The extract was characterized using TLC against the catechin marker. Then, drug-excipient interaction studies were carried out. The mixture of drug and excipients was evaluated for pre-compression parameters. With the application of 32 factorial design, chewable tablets were prepared using direct compression technique. Prepared tablets were evaluated for post-compression parameters. In vitro drug release study of the developed formulations was investigated both in intact and crushed form of tablets. Based on the in vitro performance, the best formulations were selected (F6, F7 & F8 from intact and F1, F5 & F9 from the crushed group) and subjected to various kinetic models and evaluated for Chewing Difficulty Index (CDI). The overall results revealed that the formulated chewable tablets complied with the standards and exhibited the satisfactory performance in terms of drug release, chewing difficulty index and other related parameters.

Formulation and evaluation of fast dissolving films of repaglinide solid dispersio

The aim of the research work is to formulate fast dissolving films of repaglinide solid dispersion. The major problem of repaglinide is its low solubility. To enhance the solubility of the drug repaglinide, it is made into Solid dispersion by Solvent evaporation method by using polyethylene glycol 4000 as carrier. Prepared repaglinide solid dispersion is formulated into fast dissolving films by solvent casting method by using various hydrophilic polymers like hydroxy propyl methyl cellulose E-15, polyvinyl pyrrolidone K-30 and polyvinyl alcohol in different concentration and glycerol as plasticizer. The compatibility of the drug with the excipients was confirmed by Fourier transform infrared spectroscopy studies. Various evaluation parameters were done for all the formulated films. They are Physical appearance, Surface texture, Thickness uniformity, Folding endurance, Drug-Excipient interaction studies, Disintegration study, Drug content uniformity, In-vitro release study, Permeation study, Stability study. The optimized formulation F3 has shown satisfactory disintegration time of 40 seconds and in-vitro drug release of 98.72 % within 8 minutes.

Factorial design, formulation, in vitro and in vivo evaluation of rapid orally disintegrating tablets prepared by sublimation technique using captopril as a model drug

A factorial design (23) was applied to the formulation of rapid orally disintegrating tablets, in order to investigate the feasibility of using superdisintegrant and sublimation technique on the onset of antihypertensive action of captopril. The three independent factors, superdisintegrant (Ac-di-sol) concentration (2.5% or 5%), subliming agent type (menthol or camphor) and its concentration (5% or 10%), were studied for their main effects on three dependent responses, tablet hardness, disintegration time and in vitro drug release. Statistical analysis of obtained data and optimization of formulation variables were carried out using Design-Expert® software, which selected formulation (F10), prepared with 5% Ac-di-sol and 10% camphor, that displayed suitable in range hardness (3.425 ± 0.12 Kilopond), least disintegration time (17.48 ± 1.36 Seconds) and highest in vitro drug release (99.51 ± 0.24% after 8 min), as the optimum formulation with the highest desirability (0.937). F10 was then chosen for drug-excipients interaction studies (DSC and FTIR), accelerated stability study at 40 °C and 75% RH for 3 months and in vivo evaluation against conventional captopril tablets, in hypertensive rats, using tail-cuff method. F10 showed no interaction between drug and excipients, chemical and physical stability and 15 min faster normalization of mean arterial pressure, of hypertensive rats, than conventional captopril tablets.

DEVELOPMENT AND IN VITRO EVALUATION OF 5-FLUOROURACIL NANOPARTICLES BY SALTING OUT TECHNIQUE

Objectives: At the current miserable state of the prevalence of cancers, there is a need for the development of simple technologies to prepare formulations of anticancer drugs with less economy and investment. Hence, the aim of the present work is to prepare nanoparticles of 5-fluorouracil (5-FU) by simple technique, such as salting out method.
 Methods: Nanoparticles containing 10 mg of 5-FU were prepared by salting out method using Eudragit-100 as polymer. The prepared nanoparticles were evaluated by particle size, zeta potential, in vitro drug release studies, and drug-excipient interaction studies.
 Results: Nanoparticles prepared by salting out methods showed higher dissolution rate for formulation F3 and F5 revealed high percentage release of 98.6±0.24 in 60 min and 86.5±0.39% in 120 min. Fourier transform infrared (FTIR) spectra revealed no interaction between drug and excipients used for preparation.
 Conclusion: 5-FU nanoparticles can be produced successfully by salting out method using drug to polymer (Eudragit S-100) ratio of 1:3 to possess ideal drug release characteristics and average particle size of 205.1 nm.

DEVELOPMENT AND IN VITRO EVALUATION OF PHYTOSOMES OF NARINGIN

Objective: Phytosomes are novel herbal formulations meant for design of poorly soluble flavonoids of therapeutic potential. Naringin is a flavanone with poor oral absorption and bioavailability but possess antioxidant, anti-inflammatory, antiapoptotic, anti-ulcer, antiosteoporotic, and anticarcinogenic effects. Hence, the objective of the present work is the development of phytosomes of naringin to enhance its dissolution so that its therapeutic effects can be exploited.
 Materials and Methods: Phytosomes containing 350 mg of naringin were prepared by antisolvent precipitation method and rotary evaporation method using soya lecithin as main polymer. The prepared phytosomes were evaluated by entrapment efficiency, in vitro drug release studies, and drug-excipient interaction studies.
 Results: Phytosomes made by rotary evaporation method evidenced higher dissolution values than phytosomes made by antisolvent precipitation. Formulation F7 containing 350 mg of naringin and 1400 mg of soya lecithin revealed the highest percentage release of 84.5±0.39% in 60 min and 99.7±0.24% in 120 min. The percentage of drug entrapment efficiency values was satisfactory. Fourier-transform infrared spectroscopy spectra of pure naringin and naringin phytosomes revealed no interaction between the drug and polymers used for preparation.
 Conclusion: Naringin phytosomes are produced successfully by the rotary evaporation method. Phytosomes made with 350 mg of naringin and 1400 mg of soya lecithin by rotary evaporation method are spherical with a rough outer surface and optimum release characteristics of 84.5±0.39 in 60 min to possess optimum bioavailability and 99.7% in 120 min.

FORMULATION AND DEVELOPMENT OF TRANSDERMAL DRUG DELIVERY SYSTEM OF ETHINYLESTRADIOL AND TESTOSTERONE: IN VITRO EVALUATION

Objective: The combination therapy of ethinylestradiol and testosterone in post-menopausal females has shown improved sexual response and libido. The present studies were designed to develop a suitable matrix-type transdermal drug delivery system (TDDS) of ethinylestradiol and testosterone using the polymer chitosan.Methods: Five formulations (ET1 to ET5) were developed by varying the concentration of polymer and keeping the drug load constant. Physical parameters and drug excipient interaction studies were evaluated in all the formulations. In vitro skin permeation profiles of ethinylestradiol and testosterone from various formulations were simultaneously characterized in a thermostatically controlled modified Franz Diffusion cell using HPLC. Based on the physical parameters and in vitro skin permeation profile formulation ET3 containing 30 mg/ml of chitosan was found to be the best and chosen for further studies. Optimized formulation was subjected to in vivo pharmacokinetic analysis in rats using ELISA.Results: Stability profile of patch formulation ET3 depicted stability up to 3 mo. One week skin irritation evaluation in rats indicated that formulation ET3 was nonirritating. Combination transdermal patch across rat skin showed a maximum release of 92.936 and 95.03 % in 60 h with a flux of 2.088 and 21.398 µg/cm2h for ethinylestradiol and testosterone respectively.Conclusion: The net result of this study is the formulation of a stable, non-irritating transdermal patch of ethinylestradiol and testosterone, with good bioavailability and can be used as Estrogen Replacement Therapy (ERT) in postmenopausal women.

EFFECT OF HYDROPHILIC AND HYDROPHOBIC POLYMER MATRIX ON THE TRANSDERMAL DRUG DELIVERY OF ETHINYLESTRADIOL AND MEDROXYPROGESTERONE ACETATE

Objective: The aims of the present study were to develop different matrix patches with various ratios of hydrophilic and hydrophobic polymer combinations such as ethyl cellulose (EC) and polyvinylpyrrolidone (PVP) and eudragit RL 100 (ERL) and eudragit RS 100 (ERS) containing ethinylestradiol and medroxyprogesterone acetate and to perform physicochemical characterization and in vitro permeation studies through rat skin.Methods: Six formulations (F1 to F6) were developed by varying the concentration of both hydrophilic and hydrophobic polymer and keeping the drug load constant. Physical parameters and drug excipient interaction studies were evaluated in all the formulations. In vitro, skin permeation profiles of ethinylestradiol and medroxyprogesterone acetate from various formulations were simultaneously characterized in a thermostatically controlled modified Franz Diffusion cell. The physicochemical compatibility of the drug and the polymers was studied by differential scanning calorimetry.Results: The results suggested no physicochemical incompatibility between the drug and the polymers. In vitro permeation studies were performed by using Franz diffusion cells, patches coded as F3 (ethyl cellulose: polyvinylpyrrolidone, 7.5:2.5) and F6 (eudragit RL 100 (ERL) and eudragit RS 100 (ERS), 8:2) can be chosen for further in vivo studies. The results followed Higuchi kinetics (r = 0.9953-0.9979), and the mechanism of release was diffusion mediated. Based on physicochemical and in vitro skin permeation studies of 85.64% (for F3) and 88.62% (for F6) of ethinylestradiol and medroxyprogesterone acetate.Conclusion: The developed transdermal patches are stable, non-irritating and had increased efficacy of ethinylestradiol and medroxyprogesterone acetate and therefore had a good potential for antifertility treatment.

FORMULATION AND EVALUATION OF ESOMEPRAZOLE FAST DISSOLVING BUCCAL FILMS

Objective: The present study deals with the formulation and evaluation of fast dissolving buccal films for effective treatment option in the gastroesophageal reflux disease.Methods: Esomeprazole fast dissolving buccal films are a convenient formulation of which can be taken with or without water. In the present investigation, polyvinyl alcohol and polyvinylpyrrolidone were used as film-forming agents and polyethylene glycol 400 is taken as plasticizer. Solvent evaporation method was used for the preparation of fast dissolving buccal films.Results: The films were prepared and evaluated for film thickness, folding endurance, dispersion test, drug content, and dissolution. The in vitro dissolution studies were carried out using simulated salivary fluid (pH 6.8 phosphate buffer).Conclusion: Among all the formulations, Formulation E7 was released up to 99.6% of the drug from the film within 5 min of time which exhibits faster absorption and also shows desirable characteristics of the film. The drug-excipient interaction studies WERE carried out by Fourier-transform infrared studies, differential scanning calorimetry analysis-X-diffraction studies, and scanning electron microscopic studies and the results revealed that there were no major interactions between the drugs and excipients used for the preparation of films.

Soluble starch-blended Ca2+-Zn2+-alginate composites-based microparticles of aceclofenac: Formulation development and in vitro characterization

The present article describes development of starch-blended Ca2+-Zn2+-alginate microparticles of aceclofenac for attaining gastric protection and controlled release delivery. Different formulations (F1 to F7) of microparticles were prepared by ionotropic gelation method and subjected to characterization studies. In vitro drug release studies were performed in 0.1 N HCl (pH 1.2) for initial 2 h and additional 5 h in phosphate buffer (pH 7.4). These microparticles were characterized by SEM, FTIR spectroscopy and XRD analyses. The formulation F7 (prepared using sodium alginate of 300 mg, soluble starch 250 mg, 5% CaCl2 and 1% ZnSO4) was selected as the optimized formulation, which exhibited entrapment efficiency of 85.73%, particle size of 1610 μm and viscosity of 802.16 cps. In vitro drug release from the formulation F7 revealed maximal 38% drug release within 7 h indicating sustained drug release profile from the prepared formulation. Also, in vitro swelling studies revealed maximal swelling within the period of 2 h at pH 7.4 for all these microparticles. The surface morphology studies performed using SEM showed smooth and spherical nature of the microparticles. Evaluation of drug release kinetic indicated fitting as per Korsmeyer-Peppas model and construed drug release via Fickian diffusion mechanism. Drug-excipient interaction studies using FTIR spectroscopy showed no change in characteristic peaks of the drug, while powder XRD revealed absence of sharp crystalline peaks of the drug. Overall, the present investigation corroborated successful development of microparticles of aceclofenac as an effective and cost-effective approach for oral delivery of aceclofenac.

DEVELOPMENT AND OPTIMIZATION OF ORODISPERSIBLE TABLETS OF CARVEDILOL BY COMBINATION OF SUPER-DISINTEGRANTS ADDITION AND SUBLIMATION TECHNIQUES

Objective: Objective of the present research work was to prepare orodispersible tablets of carvedilol (CDL) for dysphagic patients.Methods: Carvedilol, an anti-hypertensive drug, was chosen as a model drug in this study. Orodispersible tablets of carvedilol were prepared using different super-disintegrating agents such as crospovidone, croscarmellose sodium and sodium starch glycolate at different concentrations. The best formulation was selected based on disintegration and dissolution profile that was further taken for sublimation studies using camphor, menthol and thymol. Drug-excipients interaction studies were carried out by fourier transform infra-red (FTIR) spectrophotometer with pure drug sample and optimized formulation.Results: The orodispersible tablet formulation having 4% croscarmellose sodium disintegrated in 92 sec. Hence this formulation was considered best formulation and taken further for sublimation studies. A formulation containing 10% w/w of menthol showed disintegration time of 16 sec with more than 96.64% drug release within 15 min. Menthol leaves the porous structure as it sublimates from the tablet. This might have contributed to the decrease in disintegration time. Hence, this formulation was considered optimized.Conclusion: From this study, it can be concluded that orodispersible tablets of carvedilol may prove to be more efficacious in the treatment of hypertension particularly in dysphagic patients.

DEVELOPMENT AND CHARACTERIZATION OF GASTRORETENTIVE DRUG DELIVERY SYSTEM FOR RITONAVIR TABLETS USING NATURAL POLYMERS

ABSTRACT Objective: The present study involves preparation and evaluation of floating tablets of ritonavir for improving the drug bioavailability by prolongation of gastric residence time.Ritonavir is an antiretroviral agent used in treatment of HIV and viral diseases has been taken as a model drug in the present investigation because of its low biological half life (3-5h). Moreover it is primarily absorbed from stomach. Materials and Methods: Ritonavir floating tablets were prepared by the dry granulation technique, using guar gum and xanthan gum as polymers, sodium bicarbonate as effervescent agent, PVP as binding agent, Di calcium phosphate as diluents, Crospovidone as swelling agent and magnesium stearate as lubricant. The prepared tablets were evaluated for various physico-chemical parameters. Results: Drug-excipient interaction studies were conducted by FTIR and DSC. The results suggested that there was no incompatibility between the drug and polymers. The prepared tablets were evaluated for their physical characteristics. All the parameters were within the pharmacopoeial limits. Further, tablets were also studied for their floating properties and in vitro drug release characteristics. The tablets exhibited controlled and prolonged drug release profiles. The developed formulation was found to be stable. Conclusion: The developed floating tablets of ritonavir exhibit prolonged release upto 12 h, and thus may improve bioavailability and minimize fluctuations in plasma drug concentrations. Key words: Ritonavir, floating tablets, gastric residence time, gastroretentive drug delivery system