Enhanced Mefenamic Acid Release from Poloxamer-Silicon Dioxide Gel Filled in Hard Gelatin Capsules – An application of Liquid Semisolid Matrix Technology for Insoluble Drug

Introduction: : Liquid semisolid matrix (LSSM) technology involves the filling of drug-mixed gel in hard gelatin capsules for different applications. Methods: In continuation of our previous work on LSSM technology, 10% (w/w) of practically insoluble model drug, mefenamic acid was incorporated in gels of different poloxamers with 8% (w/w) SiO2. Gels exhibited plasticity or pseudoplasticity along thixotropy at 2 and 24 h enabling their easy filling into hard gelatin capsules without content seepage. Mefenamic acid gels prepared with L64 and L92 maintained their apparent viscosities for the study period of one month. Around 100% mefenamic acid was released within 90 min from L64- and in 150 min from L92-SiO2 gels, both with first-order kinetics. Results: In 12 month long-term stability studies, only mefenamic acid-L64-SiO gel at 30°C/65% RH indicated dispersion stability with similar rheology and release pattern to that at 2, 24 and 30 days. Conclusion: No chemical drug-polymer interactions were found in FTIR. The release of practically insoluble mefenamic acid could be enhanced from gel formulated with L64 and SiO2.

Manufacture of Hard Gelatin Capsules From a Lyophilisate of the Morus Nigra Fruit

Morus nigra L. (M. nigra L.) belongs to the Moraceae family. Traditional medicine for its physicochemical properties. To evaluate the physicochemical composition and pharmaceutical stability of hard gelatin capsules of the freeze-dried fruit of M. nigra L. The content of total phenols (CFT) and antioxidant capacity (CA) were evaluated by spectrophotometry, the content of ash, moisture, protein, fat and fiber were determined according to their own standard. The CFT and CA were 25.4 mg gallic acid equivalents/g of sample, and 74.1% inhibition, respectively. On the other hand, the values of ash, moisture, protein, fat and fiber were 4.2%, 7.9%, 3.9%, 0.5% and 3.6%, respectively. Lyophilized M. nigra fruit may be a novel candidate for the development of gelatin hard capsules and other new pharmaceutical products.

Biopharmaceutical Evaluation of Capsules with Lyophilized Apple Powder

Apples are an important source of biologically active compounds. Consequently, we decided to model hard gelatin capsules with lyophilized apple powder by using different excipients and to evaluate the release kinetics of phenolic compounds. The apple slices of “Ligol” cultivar were immediately frozen in a freezer (at −35°C) with air circulation and were lyophilized with a sublimator at the pressure of 0.01 mbar (condenser temperature, −85°C). Lyophilized apple powder was used as an active substance filled into hard gelatin capsules. We conducted capsule disintegration and dissolution tests to evaluate the quality of apple lyophilizate-containing capsules of different encapsulating content. Individual phenolic compounds can be arranged in the following descending order according to the amount released from the capsules of different compositions: chlorogenic acid > rutin > avicularin > hyperoside > phloridzin > quercitrin > (−)-epicatechin > isoquercitrin. Chlorogenic acid was the compound that was released in the highest amounts from capsules of different encapsulating content: its released amounts ranged from 68.4 to 640.3 μg/mL. According to the obtained data, when hypromellose content ranged from 29% to 41% of the capsule mass, the capsules disintegrated within less than 30 min, and such amounts of hypromellose did not prolong the release of phenolic compounds. Based on the results of the dissolution test, the capsules can be classified as fast-dissolving preparations, as more than 85% of the active substances were released within 30 min.

ПОРІВНЯЛЬНІ ДОСЛІДЖЕННЯ ПРОФІЛІВ ВИВІЛЬНЕННЯ ДОКСИЦИКЛІНУ ХІКЛАТУ З ТВЕРДИХ ЖЕЛАТИНОВИХ КАПСУЛ ПРИ ЗМІНІ ВИРОБНИКІВ ДІЮЧОЇ РЕЧОВИНИ

Comparative studies of the release profiles of doxycycline hyclate from hard gelatine capsules, developed with the active ingredient of alternative manufacturers. The object of the study is samples of the drug doxycycline hyclate in the form of hard gelatin capsules made from an API of an approved manufacturer "Kaifeng Pharmaceutical Group Co. Ltd", China and an alternative manufacturer "HebeiJiupeng Pharmaceutical Co., Ltd.", China. The study of the profiles of the release of the active substance from the drug was carried out using the "Paddle apparatus". The amount of the released substance was determined by the absorption spectrophotometry method.A drug was investigated in hard gelatin capsules of 100 mg based on the substance of doxycycline hyclate from two manufacturers "Kaifeng Pharmaceutical Group Co. Ltd", China, and "HebeiJiupeng Pharmaceutical Co., Ltd", China. It was found that according to the profile of impurities and the results of quality indicators, the substances of doxycycline hyclate from the studied manufacturers are alternative and interchangeable. To confirm the similarity of the dissolution profiles of doxycycline, 100 mg capsules were tested in accordance with the requirements of the State Pharmacopoeia Department, 2.9.3. Dissolution test, using solutions at three pH values: pH 1.0 (0.1 M HCl), pH 4.6 (acetate buffer) and pH 6.8 (phosphate physiological buffer). Comparative studies in vitro for two batches of the medicinal product established the similarity of the kinetics of the release of the active substance. The calculated values of the similarity factor are: f2 = 78.4 for a solution with pH = 1.2; f2 = 82.7 for a solution with pH = 4.6 and f2 = 75.8 for a solution with pH = 6.8. According to studies in three buffer solutions, the similarity coefficient is in the range from 50 to 100, which allows it to conclude that the studied API manufacturers can be used as alternatives for the production of the drug doxycycline hyclate in hard gelatin capsules of 100 mg. The relative standard deviation of the mean (RSD) release rate is less than 20% at the first control point and not more than 10% from the second to the last control point, indicating that the results are valid. It has been proven that the study of the dissolution profiles of solid dosage forms in vitro makes it possible to assess the risks of using APIs synthesized by various manufacturers. The obtained results of the experiment allow manufacturers of finished medicines to reasonably use alternative manufacturers of raw materials to ensure uninterrupted industrial production and meet market demand.

FORMULATION AND EVALUATION OF HARD GELATIN CAPSULES CONTAINING Bacopa Monnieri

Introduction: The present work deals the formulation of hard gelatin capsules containing granules of Brahmi (Bacopa monnieri). Bacopa monnieri is used in Ayurvedic traditional medicine to improve memory and to treat various ailments. The aim of the project is to achieve immediate release of drug from dosage form to achieve therapeutic efficacy and patient compliance. Hard gelatin capsules offer rapid drug release and protection from atmospheric oxygen. Materials and methods: In this work we have prepared the granules of Brahmi and filled into the empty hard gelatin capsule shells. The hard gelatin capsules were then evaluated for dissolution studies, disintegration study, drug content and weight variation. Results and Discussion: After dissolution study it was found that 93.46% of Brahmi was released within 90 min. The kinetics of drug release was also studied and it was found to follow Korsmeyer Peppas model.

Fabrication and Evaluation of Mini Tablet Filled Capsules to Treat Transient Ischemic Attack

In this work, mini tablets filled hard gelatin capsules were fabricated for a fixed-dose therapy for transient ischemic attack (TIA). Clopidogrel besylate (CB)-75 mg and acetyl salicylic acid (ASA)-75 mg were utilized in this work. Among the mini-tablets (MTs) clopidogrel besylate, was uncoated conventional mini-tablets, whereas acetyl salicylic acid was enteric-coated. Acetyl salicylic acid gastric irritation was overcome by using Plantago ovata seed mucilage as a binder in all mini-tablets. Both types of mini-tablets were filled in hard gelatin capsules. Clopidogrel besylate and acetyl salicylic acid compatibility with excipients used were evaluated, all the mini-tablets were judged for post-compression constraints. The prepared mini-tablets confirmed no interaction by FTIR and DSC studies. All the mini-tablets passed the physico-chemical constraints. Clopidogrel besylate was released from the dosage form within 45 min, whereas enteric-coated acetyl salicylic acid mini-tablets resist to release in an acidic environment and released within 45 min in an alkaline buffer. Even the filled capsules were also passed all the parameters evaluated. The study concludes that by using P. ovata as a binder in making tablets will resolve the issues related to gastric irritation.

COMPARATIVE STUDY ON CLINICAL EFFICACY AND SAFETY OF FORMULATED AND MARKETED MYRRH EXTRACT IN CAPSULES

Objective: The development of myrrh extract from natural origin capable of eradicating schistosomal infection has gained the interest of many scientists. Recently, myrrh extract is considered as the drug of choice from natural origin used to treat schistosomiasis. This study was performed to evaluate the safety and efficacy of hard gelatin capsules of myrrh extract in the treatment of Schistosoma mansoni compared to Mirazid which is the only herbal drug present in the market. Methods: In the present study, the clinical evaluation of different doses of formulated myrrh extract hard gelatin capsules against different grades of S. mansoni infections (mild, moderate, and heavy) was carried out and compared with marketed soft gelatin capsules Mirazid. Results: In all types of S. mansoni infection, it was clear that the efficacy of n-hexane and alcohol myrrh extracts hard gelatin capsules was higher than or equal to that of Mirazid soft gelatin capsules. Conclusion: Hard gelatin capsules of myrrh extract (mixed doses) are more effective and more economic as a pharmaceutical dosage form for pharmaceutical manufacturers than Mirazid soft gelatin capsules. Consequently, with its lower price, it can reach the poor patient which is the main patient of schistosomiasis.

Determination of the critical parameters of the technological process of obtaining solid dosage forms with dry extract and crushed roots and rootes of Scutellaria baicalensis

An important condition for obtaining a high-quality drug is the determination of critical points and parameters of the production process, which is divided into several successive stages. The aim study of the critical parameters of the production of tablets and capsules with vegetable raw materials. For this purpose, validation studies of technological processes were carried out for tablets with dry extract of Scutellaria baicalensis and hard gelatin capsules with vegetable raw materials. The subject of our research was the technological process of obtaining tablets based on dry extract of the roots and rhizomes of Baikal skullcap and hard gelatin capsules based on crushed raw materials. We have identified critical process parameters for each stage. Validation tests were carried out for certain critical process parameters and acceptance criteria were calculated. Quality control of finished tablets based on dry extract of Baikal skullcap and finished hard gelatin capsules based on crushed roots and rhizomes of Baikal skullcap was performed according to the following indicators: appearance, identification, average weight, mass uniformity, disintegration, dissolution, abrasion, microbiological purity, quantitative determination . The obtained validation data of experimental-industrial series meet the acceptance criteria, and the developed technology is reproducible and promising for further validation. On the basis of the obtained results, it can be concluded that the established critical values of the parameters of the production processes and their conditions of carrying out allow for stable and reliable production of semi-finished and finished products that meet the quality standards in accordance with regulatory documents.