Fabrication and evaluation of fast disintegrating pellets of cilostazol.

The present study was designed to formulate and develop fast disintegrating pellets of poorly soluble model drug (cilostazol) by reducing the proportion of micro-crystalline cellulose with pre-gelatinized starch (PGS), lactose and chitosan. The bioavailability enhancement of a model drug was achieved by preparing inclusion complex with Captisol® (Sulfobutyl Ether ß cyclodextrin - SBE-ß-CD). Extrusion-spheronization technique was used to formulate pellets. Placket-Burman design was used for the initial screening of most significant factors such as screen size (mm), ratio of micro crystalline cellulose: PGS + lactose + chitosan and % of HPMC which affects pellet properties. The inclusion complex of drug and Captisol® (SBE-ß-CD) was prepared by Solvent Evaporation method and were incorporated into pellets in a predefined proportion. Formulation was optimized by using 32 full factorial design, the optimized batch was selected on the basis of dependent variables such as % yield, pellet size, disintegration time and % Cumulative drug release (%CDR), the obtained results were 87.15%, 0.75 mm, 13 min and 91.024% respectively. Differential scanning calorimetry (DSC) and Fourier transform infrared spectrometry (FTIR) study revealed no significant interaction between drug and polymer. Scanning electron microscopy (SEM) confirmed uniform and spherical shaped pellets having pores on the surface which facilitates wicking action and fast disintegrating property of pellets. A design space was constructed to meet the desirable target and optimized batch. The scope of study can further extended to hydrophobic molecules which may useful due to rapid disintegration and enhanced dissolution rate.

Formulation and Optimization of Multiparticulate Drug Delivery System Approach for High Drug Loading.

The aim of the present work was to develop and optimize multiparticulate formulation viz. pellets of naproxen by employing QbD and risk assessment approach. Mixture design with extreme vertices was applied to the formulation with high loading of drug (about 90%) and extrusion-spheronization as a process for manufacturing pellets. Independent variables chosen were level of microcrystalline cellulose (MCC)-X 1, polyvinylpyrrolidone K-90 (PVP K-90)-X 2, croscarmellose sodium (CCS)-X 3, and polacrilin potassium (PP)-X 4. Dependent variables considered were disintegration time (DT)-Y 1, sphericity-Y 2, and percent drug release-Y 3. The formulation was optimized based on the batches generated by MiniTab 17 software. The batch with maximum composite desirability (0.98) proved to be optimum. From the evaluation of design batches, it was observed that, even in low variation, the excipients affect the pelletization property of the blend and also the final drug release. In conclusion, pellets with high drug loading can be effectively manufactured and optimized systematically using QbD approach.

Formulation and development of ophthalmic in situ gel for the treatment ocular inflammation and infection using application of quality by design concept.

CONTEXT: The conventional liquid ophthalmic delivery systems exhibit short pre-corneal residence time and the relative impermeability to the cornea which leads to poor ocular bioavailability. OBJECTIVE: The aim of this study was to apply quality by design (QbD) for development of dexamethasone sodium phosphate (DSP) and tobramycin sulfate (TS)-loaded thermoresponsive ophthalmic in situ gel containing Poloxamer 407 and hydroxyl propyl methyl cellulose (HPMC) K4M for prolonging the pre-corneal residence time, ocular bioavability and decreases the frequency of administration of dosage form. The material attributes and the critical quality attributes (CQA) of the in situ gel were identified. Central composite design (CCD) was adopted to optimize the formulation. MATERIALS AND METHODS: The ophthalmic in situ forming gels were prepared by cold method. Materials attributes were the amount of Poloxamer 407 and HPMC and CQA identified were Gel strength, mucoadhesive index, gelation temperature and % of drug release of both drug. RESULTS AND DISCUSSION: Optimized batch (F*) containing 16.75% poloxamer 407 and 0.54% HPMC K4M were exhibited all results in acceptable limits. Compared with the marketed formulation, optimized in situ gel showed delayed Tmax, improved Cmax and AUC in rabbit aqueous humor, suggesting the sustained drug release and better corneal penetration and absorption. CONCLUSION: According to the study, it could be concluded that DSP and TS would be successfully formulated as in situ gelling mucoadhesive system for the treatment of steroid responsive eye infections with the properties of sustained drug release, prolonged ocular retention and improved corneal penetration.

Dissolution rate improvement of telmisartan through modified MCC pellets using 32 full factorial design.

Context: Microcrystalline cellulose (MCC) is the most widely used excipient for the production of pellets but it retards the release of poorly water soluble drugs. Objective: The present investigation reports incorporation of camphor, cross carmellose sodium (CCS) and spray dried lactose (SDL) into MCC pellets to enhance the dissolution rate of telmisartan. Materials and methods: A full factorial design (32) was used in the study. Concentration of camphor and CCS was selected as independent variables whereas percentage porosity and percentage drug release at 60 min were selected as dependent variables. Pellets were produced by extrusion-spheronization technique and evaluated for percentage yield, particle size analysis, flow characteristics, percentage porosity, drug content and in vitro drug release. Contour plots and 3-D surface plots were presented for graphical expression of the results. Results and discussion: Pellet formulations exhibited acceptable morphological, flow and mechanical properties. As against to 38.54% drug release after 60 min with MCC pellets, pellets prepared with optimized formulation, composed of proper combination of MCC, SDL, camphor and CCS, released 100% drug after 60 min. Conclusion: Our study underlines the fact that dissolution of telmisartan from MCC pellets can be successfully enhanced by incorporating water soluble excipient, disintegrant and pore formers.

Formulation and evaluation of clotrimazole transdermal spray.

CONTEXT: Transdermal spray (TS) of clotrimazole (CTZ) was formulated to improve the drug transport through the skin up to 12 h to achieve the antifungal efficacy. OBJECTIVE: The aim of present study was to formulate and evaluate antifungal transdermal spray to improve the permeation of clotrimazole across the skin and to decrease the dosing frequency in fungal infection. MATERIALS AND METHODS: Different ratios of ethanol and acetone and various grades of eudragit and ethyl cellulose were evaluated according to six criteria: viscosity, drying time, stickiness, appearance and integrity on skin and water washability. Propylene glycol (PG) and polyethylene glycol 400 (PEG 400) were used in the study as plasticizer and solubilizer. The TS was evaluated for in vitro drug release, spray angle, spray pattern, average weight per dose, pH, drug content, evaporation time, leak test and antifungal efficacy study. RESULTS AND DISCUSSION: Eudragit E100 and blend of ethanol and acetone (80:20) satisfied the desired criteria. The selection of optimized batch was based on the results of in vitro drug release, spray pattern and spray angle. The optimized batch showed the spray angle <85° and uniform spray pattern. The formulation containing PG showed higher drug release than PEG 400. The inclusion of eutectic mixture consisting of camphor and menthol (1:1) showed improved drug transport through the rat skin and larger mean zone of inhibition indicating the improved antifungal efficacy. CONCLUSION: The TS of CTZ can be an innovative and promising approach for the topical administration in the fungal diseases.

Exploration of statistical experimental design to improve entrapment efficiency of acyclovir in poly (d, l) lactide nanoparticles.

OBJECTIVE: In current exploration, systematic attempts have been made to improve the entrapment efficiency of a model hydrophilic drug substance, i.e. acyclovir, in poly (d, l) lactide (PLA) nanoparticles (NPs) using a modified nanoprecipitation technique. METHODS: Formulation parameters such as drug to polymer ratio, antisolvent selection, electrolyte (NaCl) addition, pH alteration and temperature were screened to improve the entrapment efficiency of acyclovir in PLA NPs. The temperature of the system (0-5 °C), phase volume ratio (1:2), stirring speed (2000 rpm), sonication time (5 min), etc. were kept constant during the preparation of NPs. Drug to polymer ratio and electrolyte addition emerged as critical formulation parameters affecting particle size as well as entrapment efficiency. Hence, in the present investigation a 3(2) full factorial design was used to investigate the combined influence of two factors, i.e. drug to polymer ratio (X1) and the amount of electrolyte, i.e. NaCl (X2) on particle size (Y1) and entrapment efficiency (Y2). The NPs were also evaluated for drug-excipient compatibility study by employing DSC and FT-IR analysis, whereas in vitro drug release studies were performed using dialysis bag technique in phosphate buffer pH 7.4. RESULTS: Statistically significant models were evolved to predict entrapment efficiency and particle size. The effect of factors X1, X2 and [Formula: see text] was found to be statistically significant in nature. Response variables, i.e. entrapment efficiency and particle size, were simultaneously optimized using desirability function using Design Expert software. This process allowed the selection of most suitable level of factors to achieve desired level of particle size and entrapment efficiency. The results of multiple linear regression analysis revealed that for obtaining desirable particle size (less than 250 nm) and entrapment efficiency (more than 17%), the NPs should be prepared using 1:3 drug to polymer ratio and 0.04 M NaCl. Acyclovir was found to be compatible with PLA as indicated by DSC and FT-IR studies. The experimental values obtained from the optimized formulation highly agreed with the predicted values. The drug release from the optimized formulation exhibited biphasic pattern and the drug release kinetics was best explained by Weibull model. CONCLUSION: In conclusion, results of the present study demonstrated that PLA NPs with expected particle size and entrapment efficiency can be obtained by adopting the concept of quality by design.

Microemulsion-based gel of terbinafine for the treatment of onychomycosis: optimization of formulation using D-optimal design.

The aim of the present investigation was to evaluate microemulsion as a vehicle for dermal drug delivery and to develop microemulsion-based gel of terbinafine for the treatment of onychomycosis. D-optimal mixture experimental design was adopted to optimize the amount of oil (X(1)), Smix (mixture of surfactant and cosurfactant; X(2)) and water (X(3)) in the microemulsion. The formulations were assessed for globule size (in nanometers; Y(1)) and solubility of drug in microemulsion (in milligrams per milliliter; Y(2)). The microemulsion containing 5.75% oil, 53.75% surfactant-cosurfactant mixture and 40.5% water was selected as the optimized batch. The globule size and solubility of the optimized batch were 18.14 nm and 43.71 mg/ml, respectively. Transmission electron microscopy showed that globules were spherical in shape. Drug containing microemulsion was converted into gel employing 0.75% w/w carbopol 934P. The optimized gel showed better penetration and retention in the human cadaver skin as compared to the commercial cream. The cumulative amount of terbinafine permeated after 12 h was 244.65 ± 18.43 µg cm(-2) which was three times more than the selected commercial cream. Terbinafine microemulsion in the gel form showed better activity against Candida albicans and Trichophyton rubrum than the commercial cream. It was concluded that drug-loaded gel could be a promising formulation for effective treatment of onychomycosis.

Effect of Hypoproteinemia on Electrolyte Measurement by Direct and Indirect Ion Selective Electrode Methods.

Objective The aim of this study was to see the effect of hypoproteinemia on electrolyte measurement by two different techniques, that is, direct ion selective electrode (ISE) and indirect ISE. Material and Method It was an observational study in which 90 serum samples with normal protein content (Group-1) were subjected to sodium (Na + ) and potassium (K + ) measurements by direct and indirect ISE methods. In the same way, 90 serum samples with total protein < 5 g/dL (Group-2) were subjected to Na + and K + measurements by direct and indirect ISE methods. Result In samples from Group-1 patients, average Na + was 138.1 ± 4.764 mmol/L by direct ISE method and 139.3 ± 3.887 mmol/L by indirect ISE method while average K + was 4.41 ± 0.644 mmol/L by direct ISE method and 4.40 ± 0.592 mmol/L by indirect ISE method. There was no statistically significant difference in Na + and K + values measured by different methods. In samples from Group-2 patients, measured value of Na + by direct ISE and indirect ISE was 134.57 ± 5.520 mmol/L and 138.64 ± 5.401 mmol/L, respectively. Difference between these two values was statistically significant with p -value of < 0.0001, but direct ISE and indirect ISE measured values of K + was 4.146 ± 0.9639 mmol/L and 4.186 ± 0.8989, respectively, with no significant difference. Conclusion Direct and indirect ISE methods are not comparable and showing significantly different results for Na + in case of hypoproteinemia. So, it is recommended that setups like intensive care unit or emergency department, where electrolyte values have significant treatment outcome, should follow direct ISE method and should compare its previous result with the same method. Both the methods should not be used interchangeably.

Prevalence of overweight and obesity in Indian adolescent school going children: its relationship with socioeconomic status and associated lifestyle factors.

AIMS AND OBJECTIVES: Obesity and overweight have become a worldwide epidemic, and there is an urgent need to examine childhood obesity and overweight across countries using a standardized international standard. In the present study we have investigated the prevalence of obesity and overweight and their association with socioeconomic status (SES) and the risk factors like diet, physical activity like exercise, sports, sleeping habit in afternoon, eating habits like junk food, chocolate, eating outside at weekend, family history of diabetes and obesity. MATERIAL AND METHODS: The study was carried out in 5664 school children of 12-18 years of age and having different SES. The obesity and overweight were considered using an updated body mass index reference. SES and life style factors were determined using pre-tested questionnaire. RESULTS: Age-adjusted prevalence of overweight was found to be 14.3% among boys and 9.2% among girls where as the prevalence of obesity was 2.9% in boys and 1.5% in girls. The prevalence of overweight among children was higher in middle SES as compared to high SES group in both boys and girls whereas the prevalence of obesity was higher in high SES group as compared to middle SES group. The prevalence of obesity as well as overweight in low SES group was the lowest as compared to other group. Eating habit like junk food, chocolate, eating outside at weekend and physical activity like exercise, sports, sleeping habit in afternoon having remarkable effect on prevalence on overweight and obesity among middle to high SES group. Family history of diabetes and obesity were also found to be positively associated. CONCLUSION: Our data suggest that the prevalence of overweight and obesity varies remarkably with different socioeconomic development levels.

Advanced formulation design of venlafaxine hydrochloride coated and triple-layer tablets containing hypromellose.

The purpose of this research work was to develop venlafaxine hydrochloride-coated and layered matrix tablets using hypromellose adopting wet granulation technique. The granules and the tablets were characterized. The monolithic tablets were coated with different ratios of ethyl cellulose and hypromellose. The in vitro dissolution study was performed in distilled water. In the layered tablets, the middle layer containing drug was covered with barrier layers containing high viscosity grade hypromellose. Simplex lattice design was used for formulating the layered tablets. The dissolution study of the optimized batches and a reference product was carried out in 0.1 N HCl, phosphate buffer and hydroalcoholic solution. Burst drug release was exhibited by the uncoated tablets, probably due to high aqueous solubility of venlafaxine HCl. The coated tablets showed sustained drug release without burst effect. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the coated tablets. The layered tablets also exhibited sustained release without burst effect due to effective area reduction. The optimized batches showed identical drug release in 0.1 N HCl, phosphate buffer and 10% v/v aqueous alcohol. Layered tablets may well be adopted by the industry due to the possibility of achieving a high production rate.

Fabrication and evaluation of captopril modified-release oral formulation.

The present research was directed towards fabrication of modified-release captopril oral formulation. A 3(2) full factorial design was employed for optimization using captopril to Compritol ATO 888 ratio (X1) and extragranular fraction of ethyl cellulose (X2) as independent variables. The percentage drug released in 1 h (Y1) and the time required to release 80% of the drug (Y2) were selected as dependent variables. Eutectic blend of camphor and menthol was used as a solvent to facilitate the drug distribution in matrix. The optimized batch containing 50 mg captopril, 160 mg Compritol ATO 888 and 220 mg ethyl cellulose was formulated by overlapping the contour plots of Y1 and Y2. The responses Y1 and Y2 of optimized batch were 25% and 520 min, respectively. The kinetics of drug release was best explained by Korsmeyer-Peppas model. The results of artificial neural network were superior in prediction power than the factorial design for both the responses (Y1 and Y2).

Fabrication and design of transdermal fluconazole spray.

The objective of the present study was to formulate fluconazole transdermal spray for obtaining modified drug transport using eutectic mixture, ethyl cellulose, polyethylene oxide and alcohol. The formulated products were characterized. The selection of the optimized batch was done considering the results of drug transport in the first hour, the time required for 90% drug transport, viscosity and spray angle of the formulations. The inclusion of eutectic mixture, consisting of equal parts of camphor and menthol, showed improved drug transport through rat skin. The optimized batch exhibited larger mean zone of inhibition (antifungal activity), efficient in vivo activity and short term stability.

Fabrication of triple-layer matrix tablets of venlafaxine hydrochloride using xanthan gum.

The objective of present investigation was to develop venlafaxine hydrochloride-layered tablets for obtaining sustained drug release. The tablets containing venlafaxine hydrochloride 150 mg were prepared by wet granulation technique using xanthan gum in the middle layer and barrier layers. The granules and tablets were characterized. The in vitro drug dissolution study was conducted in distilled water. The tablets containing two lower strengths were also developed using the same percentage composition of the middle layer. Kinetics of drug release was studied. The optimized batches were tested for water uptake study. Radar diagrams are provided to compare the performance of formulated tablets with the reference products, Effexor XR capsules. The granules ready for compression exhibited good flow and compressibility when xanthan gum was used in the intragranular and extragranular fractions. Monolayer tablets failed to give the release pattern similar to that of the reference product. The drug release was best explained by Weibull model. A unified Weibull equation was evolved to express drug release from the formulated tablets. Lactose facilitated drug release from barrier layers. Substantial water uptake and gelling of xanthan gum appears to be responsible for sustained drug release. The present study underlines the importance of formulation factors in achieving same drug release pattern from three strengths of venlafaxine hydrochloride tablets.

Fabrication of modified transport fluconazole transdermal spray containing ethyl cellulose and Eudragit RS100 as film formers.

The present investigation was undertaken to fabricate modified transport fluconazole transdermal spray using ethyl cellulose and Eudragit RS100 as film-forming polymers. Eudragit RS100 (X(1)) and ethyl cellulose (X(2)) were selected as independent variables in 3(2) full factorial design, whereas drug transport in first hour (Y (1)) and the time required for 50% drug transport (Y(2)) were selected as dependent variables. Eutectic blend of camphor and menthol was used as permeation enhancer cum solvent for film-forming polymers. The pH, viscosity, volume of solution delivered upon each actuation, spray angle, ex-in vivo physical evaluation and in vitro drug transport of the formulated products were evaluated. The optimized batch B16 containing 5.25% w/w ethyl cellulose and 10.6% w/w Eudragit RS100 was formulated by overlapping the contour plots of Y(1) and Y(2). The pH, viscosity, volume of solution sprayed upon each actuation and spray angle of the batch B16 was 6.3, 52.9 cPs, 0.24 ml and 82.6 degrees respectively. The film of optimized batch was flexible and dermal-adhesive. The responses Y(1) and Y(2) of batch B16 were 7.91 microg/ml and 347 min respectively. The kinetics of drug transport was best explained by the Korsmeyer and Peppas model. The eutectic mixture consisting of equal parts of camphor and menthol showed improved drug permeation through shed snake skin. Short-term stability study demonstrated insignificant changes in performance characteristics.

Fabrication of modified release tablet formulation of metoprolol succinate using hydroxypropyl methylcellulose and xanthan gum.

The present investigation was undertaken to fabricate modified release tablet of metoprolol succinate using hydroxypropyl methylcellulose (HPMC) and xanthan gum as a matrixing agent. A 3(2) full factorial design was employed for the optimization of formulation. The percentage drug released at a given time (Y (60), Y (240) and Y (720)) and the time required for a given percentage of drug to be released (t (50%)) were selected as dependent variables. The in vitro drug dissolution study was carried out in pH 6.8 phosphate buffer employing paddle rotated at 50 rpm. The similarity factor (f (2)) was calculated for selection of best batch considering mean in vitro dissolution data of Seloken XL as a reference profile. It is concluded that the desired drug release pattern can be obtained by using a proper combination of HPMC (high gelling ability) and xanthan gum (quick gelling tendency). The economy of xanthan gum and faster hydration rate favors its use in modified release tablets. The matrix integrity during dissolution testing was maintained by using hydroxypropyl methylcellulose.

A Review on Enteric Coated Pellets Composed of Core Pellets Prepared by Extrusion-Spheronization.

Enteric coated dosage form bypasses the stomach and releases the drug into the small intestine. Advantages of enteric coated pellets in comparison with enteric coated tablets are a) Pellets provide rapid onset of action and faster drug release due to the smaller size than tablets and b) Pellets exhibit less residence time of acid-labile drugs in the stomach compared to tablets. Dosage form coat can be damaged by longer resistance time in the stomach. The present review summarizes the current state of enteric coated pellets where core pellets are prepared by extrusion-spheronization technique and the enteric coating is applied in a fluidized bed processor. Two approaches are involved in the preparation of core pellets. In the first approach, a mixture of drug and excipient(s)/co-processed excipient is passed through extruders to prepare core pellets. In the second approach, excipient core pellets are prepared by extrusion technique and the drug is layered onto it before the enteric coating. The excipients present in the core pellets decide immediate or extended release of drug in the intestine. The coprocessed excipient pellets provide less batch variability and provide a platform for layering of many drugs before enteric coating. Some patents included enteric coating pellets [CN105456223 (A), CN105596310 (A), CN105616371 (A), CN105663095 (A), CN101611766B, CN106511862 (A), CN106668018 (A), CN106727381 (A), CN106924222 (A), TW200624127 (A), US 2017/0165248A1, US 2017/0224720A1] are discussed.

Screening of Sacrificial Excipients for Arresting Devitrification of Itraconazole from Solid Dispersion.

OBJECTIVES: The aim of the present investigation was to develop a solid dispersion of itraconazole (ITR) using sacrificial excipients like pregelatinized starch and spray-dried lactose alongside hydroxypropyl methylcellulose and Poloxamer 188, thereby arresting the conversion of the amorphous form of ITR to crystalline form, and to assess the dissolution stability of an amorphous form of the drug during short-term storage. MATERIALS AND METHODS: ITR-loaded solid dispersions were prepared by kneading. Formulation optimization was achieved by using a 24 full factorial design on the basis of cumulative percent drug released at t30, t60, and t120 min. An artificial neural network (ANN) was also applied as a statistical tool for obtaining better predictive ability and the outcomes of the ANN were compared with that of Design-Expert software. RESULTS: The spectral data revealed no drug-carrier interactions. The P-X-ray diffraction study of the optimized batch showed a decrease in the crystallinity of drug as compared to the untreated drug. The in vitro dissolution studies of the optimized batch showed higher dissolution (92% at 120 min) in comparison to the other formulations. The dissolution stability study was performed at 40°C and 75% relative humidity for 90 days for the optimized formulation. The results of the optimized batch showed insignificant changes in cumulative percentage drug release during storage. CONCLUSION: Dissolution stability could be attributed to the presence of sacrificial excipients as they tend to absorb moisture during storage and possibly get converted into crystalline form, thereby minimizing the recrystallization of ITR.

Development of Biodegradable Injectable In situ Forming Implants for Sustained Release of Lornoxicam.

OBJECTIVE: The focus of this study was to develop in situ injectable implants of Lornoxicam which could provide sustained drug release. METHODS: Biodegradable in situ injectable implants were prepared by polymer precipitation method using polylactide-co-glycolide (PLGA). An optimized formulation was obtained on the basis of drug entrapment efficiency, gelling behavior and in vitro drug release. The compatibility of the formulation ingredients were tested by Fourier transform infrared (FT-IR) spectroscopy, and differential scanning colorimetry (DSC). SEM study was performed to characterize in vivo behavior of in situ implant. Pharmacokinetic study and in vivo gelling study of the optimized formulation were performed on Sprague-Dawley rats. Stability testing of optimized formulation was also performed. RESULTS: The drug entrapment efficiency increased and burst release decreased with an increase in the polymer concentration. Sustained drug release was obtained up to five days. SEM photomicrographs indicated uniform gel formation. Chemical interaction between the components of the formulation was not observed by FT-IR and DSC study. Pharmacokinetic studies of the optimized formulation revealed that the maximum plasma concentration (Cmax), time to achieve Cmax (Tmax) and area under plasma concentration curve (AUC) were significantly higher than the marketed intramuscular injection of lornoxicam. Stability study of optimized batch showed no change in physical and chemical characteristics. CONCLUSION: Lornoxicam can be successfully formulated as in situ injectable implant that provides long-term management of inflammatory disorders with improved patient compliance.

Design of a potential colonic drug delivery system of mesalamine.

The aim of the present investigation was to develop a site-specific colonic drug delivery system, built on the principles of the combination of pH and time sensitivity. Press-coated mesalamine tablets with a coat of HPMC E-15 were over-coated with Eudragit S100. The in vitro drug release study was conducted using sequential dissolution technique at pH 1.2, 6.0, 7.2 and 6.4 mimicking different regions of gastrointestinal tract. The optimized batch (F2) showed less than 6% of drug release before reaching colonic pH 6.4 and complete drug release was obtained thereafter within 2 hr. A short-term dissolution stability study demonstrated statistical insignificant difference in drug release.

A novel solid dosage form of rifampicin and isoniazid with improved functionality.

The aim of the present investigation was to develop a novel dosage form of rifampicin and isoniazid to minimize degradation of rifampicin in acidic medium and to modulate the release of rifampicin in the stomach and isoniazid in the intestine. Gastroretentive tablets of rifampicin (150 mg) were prepared by the wet granulation method using hydroxypropyl methylcellulose, calcium carbonate, and polyethylene glycol 4000. The granules and tablets of rifampicin were characterized. Hard gelatin capsules (size 4) containing a compacted mass of isoniazid (150 mg) and dicalcium phosphate (75 mg) were enteric coated. Two tablets of rifampicin and 1 capsule (size 4) of isoniazid were put into a hard gelatin capsule (size 00). The in vitro drug release and in vitro drug degradation studies were performed. Rifampicin was released over 4 hours by zero-order kinetics from the novel dosage form. More than 90% of isoniazid was released in alkaline medium in 30 minutes. The results of dissolution studies with the US Pharmacopeia XXIII method revealed that a substantial amount of rifampicin was degraded from the immediate release capsule containing rifampicin and isoniazid powder owing to drug accumulation in the dissolution vessel and also to the presence of isoniazid. The degradation of rifampicin to 3-formyl rifampicin SV (3FRSV) was arrested (3.6%-4.8% degradation of rifampicin at 4 hours) because of the minimization of physical contact between the 2 drugs and controlled release of rifampicin in acidic medium in the modified Rossett-Rice apparatus. This study concludes that the problem of rifampicin degradation can be alleviated to a certain extent by this novel dosage form.