Design, Formulation and Physicochemical Evaluation of Clotrimazole Chewing Gum

Background: Oral candidiasis is widespread in the patients with immunodeficiency diseases. Chewing gums are considered as mobile drug delivery systems that affected locally or systemically via the oral cavity. This study aimed to develop and evaluate the formulation of clotrimazole chewing gums for patients having oral candidiasis. Materials and Methods: Fourteen formulations (F) were designed by Design-Expert, version 7. These formulations were different in the amount of gum bases and sweeteners. Gum bases of elvasti, 487, stick, and fruit C were heated up to 70°C. Clotrimazole powder, sugar, liquid glucose, glycerin, mannitol, xylitol, and maltitol as well as different flavoring agents were added to the gum bases at 40°C. Content and weight uniformity, organoleptic properties evaluation, releasing the active ingredient in the phosphate buffer pH, 6.8, and taste evaluation were analyzed by Latin square analysis. Also, the mechanical test was done on F13 and F14 formulations. Results: F14 was the best formulation in terms of organoleptic properties. This formulation had suitable size, hardness, softness, and lack of adhesion to teeth. F14 formulation released 89% and 97% of clotrimazole after 30 and 45 minutes, respectively. F14 content uniformity and weight variations were 9.83±0.086 mg and 1.14±0.09 g, respectively. F14 evaluation of mechanical properties showed Young’s modulus about 0.32 MPa, and yield point occurred at the stress of 0.599 MPa and strain of 4.1%. Conclusion: F14 was chosen according to its physicochemical and organoleptic properties. F14 had adequate hardness, lack of adhesion to the teeth, suitable size, and best drug release. Tutti Frutti was a proper flavoring agent for clotrimazole gum formulations.[GMJ.2021;10:e1084]

Tablet Formulation Studies on Recrystallized Active Pharmaceutical Ingredients of Valsartan and Olmesartan Medoxomil

Both the Valsartan (VAL) and Olmesartan medoxomil (OLM) are widely prescribed anti-hypertensive agents with angiotensin II type I receptor antagonistic activity. Both VAL and OLM are type of BCS class II drugs and having a low and variable oral bioavailability. Recrystallization of VAL and OLM from different organic solvents improved its aqueous solubility and thereby in vitro dissolution properties. In the present investigation, tablets containing Valsartan (VAL), Olmesartan medoxomil (OLM and) recrystallized products were prepared by direct compression method and evaluated for drug content, uniformity of weight, hardness, friability, disintegration time and dissolution properties. All the tablets fulfilled the compendial requirements with regarding to weight variation, friability and disintegration time etc for immediate release tablets. The DP15 (drug percent dissolved at 15 min) values for V-1 (tablets of VAL), V-4 (tablets of methanol recrystallized product with crospovidone as disintegrant) and DIOVAN™ 40mg tablet formulations are 45.97, 98.95 and 82.65 respectively and V-4 formulation showed higher dissolution rate when compared to other formulations. The DP15 values of O-1(tablets of OLM), O-4 (tablets of acetonitrile recrystallized product with crospovidone as disintegrant and OLMY™ (20mg) tablet formulations are 29.25, 99.93 and 84.82 respectively. O-4 tablet formulations showed higher dissolution rate when compared to other tablet formulations. Keywords: Valsartan, Olmesartan medoxomil, Recrystallization, Aqueous solubility

A Hybrid Model to Predict Formulation Dependent Granule Growth in a Bi-Component Wet Granulation Process

In this study, a hybrid modeling framework was developed for predicting size distribution and content uniformity of granules in a bi-component wet granulation system with components of differing hydrophobicities. Two bi-component formulations, (1) ibuprofen-USP and micro-crystalline cellulose and (2) micronized acetaminophen and micro-crystalline cellulose, were used in this study. First, a random forest method was used for predicting the probability of nucleation mechanism (immersion and solid spread), depending upon the formulation hydrophobicity. The predicted nucleation mechanism probability is used to determine the aggregation rate as well as the initial particle distribution in the population balance model. The aggregation process was modeled as Type-I: Sticking aggregation and Type-II: Deformation driven aggregation. In Type-I, the capillary force dominant aggregation mechanism is represented by the particles sticking together without deformation. In the case of Type-II, the particle deformation causes an increase in the contact area, representing a viscous force dominant aggregation mechanism. The choice between Type-I and II aggregation is determined based on the difference in nucleation mechanism that is predicted using the random forest method. The model was optimized and validated using the granule content uniformity data and size distribution data obtained from the experimental studies. The proposed framework predicted content non-uniform behavior for formulations that favored immersion nucleation and uniform behavior for formulations that favored solid-spreading nucleation.

RP-HPLC Method Development and Validation for the Estimation of Sacubitril and Valsartan in Pharmaceutical Dosage Form

A new, economical, simple, accurate, and precise RP-HPLC method was developed for simultaneous assay and content uniformity determination of Sacubitril and Valsartan in bulk and pharmaceutical dosage form. The separation of Sacubitril and Valsartan was achieved within 6 minutes on Phenomenex Luna C18 250 mm x 4.6mm and 5µm Particle Size, column using Acetonitrile: Methanol: Water (30:55:15% v/v/v) as the mobile phase. Detection was carried out at 250 nm wavelength. The retention time of Sacubitril and Valsartan was found to be 2.361 and 3.304 min, respectively. The validation of the developed method was performed in terms of specificity, accuracy, precision, linearity, the limit of detection, the limit of quantification as mentioned in International Conference on Harmonization (ICH) guidelines. The method showed adequate sensitivity concerning linearity, accuracy, and precision over the range 12-36 μg/ml and 13-39 μg/ml for Sacubitril and Valsartan, respectively. The percentage recoveries obtained for Sacubitril and Valsartan were found to be in the range of 98.00 – 102.00 %. The proposed method is suitable for use in quality-control laboratories for quantitative analysis.

Formulation and Evaluation of Mucoadhesive Buccal Tablets of Anti-Diabetic Drug using 23 Factorial Design

The aim of the present study involved the formulation and evaluation of mucoadhesive buccal tablets of anti-diabetic drug gliclazide, Mucoadhesive buccal tablets of Gliclazide are prepared by direct compression method In this present investigational research work the mucoadhesive buccal tablets of gliclazide is prepared separately employing 23 randomized full factorial design by using xanthan gum, carbopol-934, HPMC-E15LV, In this experimental model, target is to determine how the t90% of drug release and mucoadhesive characters can be affected by adjusting three parameters, concentration of polymers xanthan gum, HPMC-E15LV, carbopol-934, of the mucoadhesive buccal tablets. 2 3 full factorial studies were designed to determine the interaction of three independent variables at two levels (low and high level concentration) The tablets were tested for weight variation, hardness, surface pH, drug content uniformity, swelling index, mucoadhesion strength and in-vitro drug release study, Ex- vivo mucoadhesion time. From the drug release studies it was found that formulation H4 containing has good drug release when compared to other formulations.

Formulation and Characterization of Fast Dissolving films of Etoricoxib

Etoricoxib belongs to a class of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). Etoricoxib acts by reducing the pain and swelling (inflammation) in the joints and muscles of people older than 16 years of age and older patients with osteoarthritis, rheumatoid arthritis, ankylosing spondylitis and gout. The present study was aimed to formulate fast dissolving oral films to enhance bioavailability, avoid presystemic metabolism and fast onset of action. The Preformulation studies such as Micromeritics, melting point, partition coefficients, UV spectroscopy, thin layer chromatography, loss on drying were carried out. The fast dissolving oral film was successfully fabricated by solvent casting method. Oral film was fabricated using PVA and PVP polymer. The prepared films were evaluated for Organoleptic evaluations, film weight, thickness, folding endurance, tensile strength, drug content uniformity of films, surface pH, disintegration time and in-vitro dissolution studies and SEM study. The formulation F8 has shown disintegration time of 22±1 seconds and is more promising, showed drug release in phosphate buffer 6.8 pH 86.33% in 10 min. Hence formulation F8 was selected as best formulation. In the stability testing all films stored at elevated temperature showed slight change in pH, other parameters were found to be unchanged.

Physicochemical Evaluation of Diploknema butyracea Seed Extract and Formulation of Ketoconazole Ointment by Using the Fat as a Base

The fat obtained from the ripened seeds of Diploknema butyracea is widely used as a vegetable oil in rural areas of Nepal. This study was aimed for the physicochemical evaluation (acid value, iodine value, saponification value, peroxide value, ester value, pH, and liquefaction point) of the Diploknema butyracea seed extract (chyuri fat) and the formulation of 2% w/w ketoconazole ointment by using it as a base. All the physicochemical parameters were determined quantitatively by using the method of Indian Pharmacopoeia (IP), volume-I. By fusion method, 3 different formulations F-A, F-B, and F-C were prepared, in which different proportions of chyuri fat, polyethylene glycol 6000 (PEG 600), Tween 80, and propylene glycol were used as an ointment base. Various quality parameters such as spreadability, extrudability, viscosity, smoothness, pH, average fill weight, assay, content uniformity, accelerated stability, and drug release profiles were determined. HPLC was used for the determination of ketoconazole content in the ointment formulations. Physicochemical evaluation of the chyuri fat ensured its suitability for industrial purpose. The active ingredient release profile of formulations F-A (87.71%), F-B (88.89%), and F-C (91.09%) after 5 hours were within acceptable range along with other parameters. Assay of the formulations F-A, F-B, and F-C were reported to be 103.01, 107.9, and 102.45%, respectively. Overall, evaluation of the formulation F-A, prepared by using chyrui fat only, gave satisfactory results and most of the parameters were statistically similar ( p > 0.05 ) to the F-B and F-C formulated by incorporating a certain proportion of synthetic base. Thus it can be concluded that chyuri fat can be the best alternative to replace the expensive synthetic base.

Blend Segregation in Tablets Manufacturing and Its Effect on Drug Content Uniformity—A Review

Content uniformity (CU) of the active pharmaceutical ingredient is a critical quality attribute of tablets as a dosage form, ensuring reproducible drug potency. Failure to meet the accepted uniformity in the final product may be caused either by suboptimal mixing and insufficient initial blend homogeneity, or may result from further particle segregation during storage, transfer or the compression process itself. This review presents the most relevant powder segregation mechanisms in tablet manufacturing and summarizes the currently available, up-to-date research on segregation and uniformity loss at the various stages of production process—the blend transfer from the bulk container to the tablet press, filling and discharge from the feeding hopper, as well as die filling. Formulation and processing factors affecting the occurrence of segregation and tablets’ CU are reviewed and recommendations for minimizing the risk of content uniformity failure in tablets are considered herein, including the perspective of continuous manufacturing.