FORMULATION AND IN VITRO–IN VIVO PHARMACOKINETIC EVALUATION OF CARDIOVASCULAR DRUG-LOADED PULSATILE DRUG DELIVERY SYSTEMS

Objective: This study is to formulate Nebivolol into a Pulsatile liquid, solid composite compression coated tablet, which will delay the release of the drug in early morning hypertension conditions. Methods: The liquid, solid composite tablet was formulated and compressed with the ethylcellulose coating polymer. The percent in vitro drug release of the liquid solid composite compressed tablet was tested. Based on disintegration time and wetting time, the LCS2, LCS3, LSC6, LCS7 and LCS12 formulations were found to be the optimized solid-liquid compacts fast-dissolving core tablet formulations, which may be excellent candidates for further coating with polymer to transfer into press coated pulsatile tablet formulations. Coating the core tablet with varying ethyl cellulose concentrations resulted in five different formulations of the pulsatile press-coated tablet (CT1, CT2, CT3, CT4, CT5). In vitro drug release, in vitro release, kinetic studies, in vivo pharmacokinetic and stability tests were all performed for the prepared pulsatile press coated tablet. Results: CT3 tablets are coated with ethyl cellulose polymer, which shows maximum controlled drug release from the core tablet i.e. 96.34±1.2% at 8th h. It shows there was an efficient delay in drug release form core tablet i.e. up to 3 h, followed by the maximum amount of drug release of 96.34±2.4 at 8h. Which shows the core drug will be more efficiently protected from the gastric acid environment 1.2 pH, duodenal environment 4.0 pH and release drug only in the small intestine. Conclusion: According to the findings, CT3 Pulsatile press-coated tablet increased the bioavailability of Nebivolol by 3.11 percent.

FORMULATION DEVELOPMENT AND EVALUATION OF CHRONOMODULATED DRUG DELIVERY SYSTEM BY ZAFIRLUKAST

Objective: The main objective of the present study was to formulate and evaluate a time-controlled single-unit oral pulsatile drug delivery system containing Zafirlukast for the prevention of nocturnal asthma attacks. To provide time-scheduled drug release for Asthma disease. It is used for preventing asthmatic attacks at early morning. Pulsatile release dosage form is increasing patient compliance by reducing the dosing frequency, especially in the early morning. Methods: Core tablets were prepared by incorporating different concentrations of natural and synthetic super disintegrants. Drug-containing core tablets (ZC1-ZC15) with different compositions of natural super disintegrants (Plantago ovata seed powder, Locust bean gum) synthetic super disintegrants (Sodium starch glycolate (SSG), Cross carmellose sodium (CCS), Crospovidone (CP)) were prepared by direct compression technique. The core tablets were subjected to pre-formulation, physicochemical and In vitro drug release studies. The fast disintegrating core tablet formulation was selected and press-coated tablets (P1-P11) were prepared with different compositions of hydrophobic polymers Eudragit RS100, Eudragit RL 100, Ethylcellulose and hydrophilic polymers Hydroxypropyl methylcellulose K4M, K100M. The optimized formulation was selected and quantified based on in vitro drug release profile in simulated gastric and intestinal fluids. Results: The pre and post-compression parameters of tablets were also found to be within limits. Formulation ZC5 with 16 mg of Locust bean gum showed the least disintegrating time, i.e., 22.13 sec, and was selected as the best immediate release core tablet. The press-coated tablet formulation P8 having 62.5 mg Eudragit RS100 and 62.5 mg of HPMC K4M in ratio 1:1 over the core tablet ZC5 showed rapid and drug release nearly after 4 h lag time and 98.86 % up to 12 h. Accelerated stability studies of the optimized formulation P8 indicated no significant difference in release profile after 3 mo. Conclusion: The in vitro dissolution study showed that lag time before drug release was highly affected by the coating amount level and nature of coating polymer used. Time-controlled pulsatile release tablets can be prepared using press-coating techniques.

Formulation development and evaluation of duloxetine extended-release tablets

Duloxetine is an anti-depressant drug which is used in depression. The aim of present investigation was to prepare an ER tablet of duloxetine with similar dissolution profile matching to Effexor ER. An immediate release core tablet of 100mg was prepared and it was compression coated using HPMC matrix system. HPMC of three viscosity grades i.e., K4M, K15M, K100M and different concentrations of 15% polymer, 25% polymer, 35% polymer & 45% polymer were taken. With the above polymers by using wet granulation and direct compression process 11 formulations were prepared. The data obtained from in vitro drug release was used to determine the similarity factor between marketed and optimized product. Out of all F11 formulation (K15M 35% polymer) is optimized and is matching with the marketed product.

FORMULATION AND EVALUATION OF DUAL-LAYERED OSMOTIC PUMP CONTROLLED-RELEASE TABLETS OF CEFIXIME

Background: This study aims to formulate, optimize and evaluate the osmotic tablet of cefixime. It improves the site specification and provides the controlled release of drug once – a – day through this drug delivery system. Cefixime assumes a significant part in dissolvability restricts other than dissolvable sort. It might increase the bioavailability of drugs by the preparation of the osmotic tablet. Method: The forming core tablet does a formulation of Controlled Porosity Osmotic Tablets (CP1 – CP9) using an ingredient like sodium chloride, PVP K30, Microcrystalline cellulose various ratios. The coating of the core tablet is done by Cellulose Acetate, PEG 400, with statistical ratios. Result: On depending upon the various evaluation parameters like hardness, diameter, friability, weight variation, content uniformity, In vitro release, CP9 formulation gave better consequence. The percentage of drug release is >95%. The optimized CP9 batch showed a maximum correlation of 0.992 with a zero-order drug release kinetic model. Conclusion: A controlled release formulation of cefixime based on osmotic technology, were developed. The release from the developed formulation was independent of pH and agitational intensity of the release media; the formulation fitted well into zero-order kinetics, indicating the release to be drug load independent. Drug release was directly proportional to the initial pore level but inversely related to the membrane weight. The release was inversely associated with the release media's osmotic pressure, confirming osmotic pumping as the central mechanism of release.

Formulation and Evaluation of Bio-adhesive Pulsatile Drug Delivery System of Telmisartan

The main objective of this study was to formulate and evaluate of Bio-adhesive pulsatile drug delivery system of Telmisartan, an anti-hypertensive drug in order to achieve better therapeutic efficacy and patient compliance. The approach of combination of bio-adhesive pulsatile formulation is suitable for gastro retention and time specific drug delivery. The study was carried by preparation of fast disintegrating core tablet followed by incorporation of core tablet to design bio-adhesive pulsatile tablet by press coating. The press coated tablet was prepared with the polymersethyl cellulose and carbopol. The formulation was evaluated for precompression and post compression parameters, lag time, drug release and bio-adhesive study. All evaluation parameters were found within limits. The lag time expected for this disease was 8 hours as need of drug release for this disease was more likely to act in early morning. The 8 hour lag time was obtained in optimized formulation which has shown muco-adhesion for the same period. Thus bio-adhesive pulsatile drug delivery system could be the best precautionary alternative for the drugs having maximum absorption in stomach and used for diseases which follows circadian rhythm.

Analisis Penyebab dan Solusi Rekonsiliasi Finished Goods Menggunakan Hipotesis Statistik dengan Metode Pengujian Independent Sample T-Test di PT.Merck, Tbk.

Merck, Tbk. merupakan perusahaan manufaktur yang bergerak di bidang pembuatan obat dengan memproduksi obat yang dituju untuk pasar over-the-counter (OTC) seperti Sangobion dan Neurobion dan juga pasar obat resep untuk rumah sakit. Berdasarkan Packaging Work Sheet (PWS) dari produk “X” yang diproduksi di PT. Merck, Tbk. ditemukan rekonsiliasi pada finished goods yang melebihi spesifikasi yang telah ditentukan sebelumnya oleh perusahaan. Rekonsiliasi merupakan perbedaan antara jumlah material yang masuk dengan material yang keluar sehingga jika rekonsiliasi melebihi yang seharusnya maka PT. Merck, Tbk. dapat mengalami kerugian karena jumlah material yang jadi tidak sesuai dengan material yang diproduksi. Berdasarkan permasalahan yang terjadi, maka penulis melakukan pengolahan data menggunakan hipotesis statistik dengan menggunakan metode pengujian Independent Sample T-Test untuk mengetahui proses produksi apa yang berpotensi menyebabkan rekonsiliasi pada finished goods produk “X”. Dengan diketahuinya penyebab dari rekonsiliasi maka dapat dicari solusi yang tepat untuk mengatasi rekonsiliasi tersebut. Dari pengolahan data yang dilakukan, ditemukan bahwa terdapat perbedaan secara nyata antara berat rata-rata core tablet dengan berat coated tablet yang menandakan bahwa proses sugar coating berpengaruh secara signifikan terhadap variasi berat yang berpotensi menyebabkan rekonsiliasi. Oleh karena itu, ditentukan solusi yang tepat untuk memperbaiki proses tersebut.

Multilayer-Coated Tablet of Clopidogrel and Rosuvastatin: Preparation and In Vitro/In vivo Characterization

The acid lability of rosuvastatin hinders the preparation of mixed combination formulations of rosuvastatin with acidic drugs such as clopidogrel. Therefore, the purpose of this study was to develop a multilayer-coated tablet that avoids physicochemical interactions between rosuvastatin and clopidogrel. Among the tested hydrophobic materials, glyceryl behenate was most effective at inhibiting the production of lactone, the acid degradation product of rosuvastatin. Therefore, the multilayer-coated tablet included a hydrophobic separation layer consisting of glyceryl behenate between the clopidogrel core tablet and the rosuvastatin coating layer. In order to prevent delayed dissolution by the stable hydrophobic separation layer, crospovidone was added into the clopidogrel core tablet as an effective disintegrant. Copovidone was also added to the coating layer of rosuvastatin, achieving a dissolution profile comparable to that of the reference drug, Crestor®. The resulting multilayer-coated tablet exhibited similar pharmacokinetic profiles to those of reference drugs (Plavix® and Crestor®) in beagle dogs, and there was no statistically significant difference in the maximum plasma concentration (Cmax), the time to reach the maximum plasma concentration (Tmax), or the area under the plasma-concentration time curve (AUC) between the test and reference formulations. The storage stability tests showed that the amounts of acid degradation products and total impurities were comparable to that of the reference drug. In conclusion, the present study successfully developed a stable multilayer-coated tablet containing both clopidogrel and rosuvastatin that may improve the patient compliance in combination therapy for cardiovascular diseases.

FORMULATION AND EVALUATION OF PRESS COATED TABLETS OF LANSOPRAZOLE

Objective: Lansoprazole an proton pump inhibitor, degrades in acidic environment, hence protection of drug is done by coating the drug with enteric coating polymers. The aim and objective of the present study was to prepare enteric coated delayed release tablets of lansoprazole by using press coating technique. Methods: Core tablets were prepared by direct compression and evaluated for their physico-chemical properties. Press coated tablets were formulated by using different combinations of ethyl cellulose, HPMC E15 and HPMC K4M as a coating layer. Core and coated tablets were optimized by dissolution studies. Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies were performed to know the compatibility of drug with various excipients. Surface morphology and uniformity of coat was evaluated by Scanning electron microscopy (SEM). Stability of optimized formulation was evaluated according to ICH guidelines. Results: Among the various formulations F5 containing ethyl cellulose: HPMC E15 (10:90) and F9 containing ethyl cellulose: HPMC K4M (25:75) were optimized based on the better drug release within 8 h. DSC studies and FTIR studies revealed compatibility of drug with excipients. Obtained SEM photographs of tablets showed that the surface of core tablet is uniformly coated with coat by press coating. Stability studies showed that the formulations were stable. Conclusion: As a result, delayed release press coated tablets developed in this study delivered lansoprazole in the intestine and protected the drug from degradation.